Skip to main content Accessibility help
×
Home
Hostname: page-component-78bd46657c-zhxtg Total loading time: 0.391 Render date: 2021-05-08T14:26:10.569Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": false, "newCiteModal": false, "newCitedByModal": true }

Selenium level is associated with apoE ε4 in rural elderly Chinese

Published online by Cambridge University Press:  12 March 2009

Sujuan Gao
Affiliation:
Department of Medicine, Indiana University School of Medicine, 410 West 10th Street – Suite 3000, Indianapolis, IN 46202-2872, USA
Yinlong Jin
Affiliation:
Institute for Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China
Kathleen S Hall
Affiliation:
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA
Chaoke Liang
Affiliation:
Institute for Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China
Frederick W Unverzagt
Affiliation:
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA
Feng Ma
Affiliation:
Institute for Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China
Yibin Cheng
Affiliation:
Institute for Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China
Jianzhao Shen
Affiliation:
Department of Medicine, Indiana University School of Medicine, 410 West 10th Street – Suite 3000, Indianapolis, IN 46202-2872, USA
Jingxiang Cao
Affiliation:
Institute for Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China
Janetta Matesan
Affiliation:
Department of Medicine, Indiana University School of Medicine, 410 West 10th Street – Suite 3000, Indianapolis, IN 46202-2872, USA
Ping Li
Affiliation:
Sichuan Provincial Center for Disease Control and Prevention in China, Chengdu, People’s Republic of China
Jianchao Bian
Affiliation:
Shandong Institute for Prevention and Treatment of Endemic Disease in China, Jinan, People’s Republic of China
Hugh C Hendrie
Affiliation:
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA Indiana University Center for Aging Research, Indianapolis, IN, USA Regenstrief Institute, Inc., Indianapolis, IN, USA
Jill R Murrell
Affiliation:
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
Corresponding
E-mail address:
Rights & Permissions[Opens in a new window]

Abstract

Objective

Se is an essential trace element in human nutrition associated with antioxidant activity. Previous studies on predictors of toenail Se or serum Se have mostly concentrated on demographic factors such as age and gender. The present paper examines the association between apoE genotype and Se levels in nail samples in a rural elderly Chinese cohort.

Design

Two thousand Chinese aged 65 years and over from four counties in China were enrolled in a cohort to study the association of Se with cognitive decline. Nail samples were collected from each participant and analysed for Se levels. Dietary Se intake was estimated from an FFQ using Se contents measured in food items collected from each village. Blood samples on filter cards were collected and analysed for apoE genotype. Mixed-effect models were constructed with nail Se level as the dependent variable and each village as the random effect, which controlled for the potential confounding effect from correlation in Se measures obtained from participants residing in the same village.

Results

In this elderly Chinese cohort, carriers of the apoE ε4 allele had significantly lower Se levels measured in nail samples than non-carriers after adjusting for other significant covariates and controlling for estimated dietary Se intake. There was no significant difference between the two genotypes on estimated Se dietary intake (P = 0·6451).

Conclusions

Future studies are needed to examine the mechanism underlying the association between the apoE ε4 allele and Se levels, including the role of oxidative stress and that of reduced lipid metabolism in the apoE ε4 carriers.

Type
Research Paper
Copyright
Copyright © The Authors 2009

Se is an essential trace element in human nutrition associated with the activity of the antioxidant enzyme glutathione peroxidase. It is considered to be a protective agent against free radicals through enhanced enzyme activity. Associations between low Se and increased risk in various disease indices (cancer, CVD, reproduction and neonatal health, asthma) have been reported(Reference Flatt, Pearce, Thomson, Sears, Robinson and Beasley1, Reference Rayman2).

There is increased interest in using Se as a biomarker for various cancer outcomes(Reference Niskar, Paschal, Kieszak, Flegal, Bowman, Gunter, Pirkle, Rubin, Sampson and McGeehin3, Reference Vogt, Ziegler, Patterson and Graubard4). Measuring Se intake in large cohort studies is often difficult because populations are often mobile and consume foods that were produced and prepared in different areas of the world. Se content in foods, especially grain, is highly variable depending on the Se content of the soils in which they are grown(5). Moreover, supplements containing Se are often ingested particularly by health-conscious individuals, further confounding the results. The rural elderly Chinese population represents a unique opportunity for studying Se exposure. The rural Chinese are unusually stable with most living in the same village throughout their entire life and consuming food that is locally grown. In addition, it is rare for these villagers to take dietary supplements. Chinese scientists have assembled extensive data on Se distributions in many parts of the country; hence it is possible to select sites with differing Se levels so that an extended range can be achieved to maximize statistical power for detecting potential associations. We have recruited a cohort of 2000 elderly Chinese from four rural counties to study Se level and its association with various health outcomes(Reference Gao, Jin and Hall6).

The apoE gene is involved in lipoprotein metabolism and is a risk factor for Alzheimer’s disease and cardiovascular disorders. There are also previous reports that an Se-deficient diet or targeted removal of a gene that causes complete loss of selenoprotein expression results in increased plasma cholesterol concentration with an increase in apoE protein(Reference Stone, Stewart, Nicholas and Pavuluri7Reference Sengupta, Carlson, Hoffmann, Gladyshev and Hatfield9). Previous studies on predictors of toenail Se or serum Se have mostly concentrated on demographic factors such as age and gender. In the present paper, we examine the association between apoE genotype and Se levels measured in nail samples.

Methods

Study population

Two thousand Chinese aged 65 years and over from four counties in China were enrolled in the study. Two sites were from Sichuan Province in south-west China and the other two sites were from Shandong Province in eastern China. Since Chinese scientists have mapped Se distribution in many parts of the country, these two provinces were selected because of the varying Se levels within each province. Prior to final site selection, Chinese investigators travelled to several candidate sites collecting demographic information to ensure the local elderly population was large enough to provide a sample of 500 elderly subjects. Samples of grain (corn, rice and wheat), soil, water and nail clippings from randomly selected individuals at each candidate site were also collected and analysed for Se and other trace elements. The goal was to have two sites within one province that differed in Se levels but were similar in trace element measures and other potential confounders. Sites with known endemic diseases were excluded from consideration.

Twenty-two villages were surveyed in the present study. For each village included in the study, the Chinese investigators and a team of interviewers who were employees of provincial and county Centers for Disease Control travelled to the area, established a temporary headquarters and conducted a complete census of residents over the age 65 years in the area. They enrolled eligible residents by going door-to-door, obtaining informed consent before conducting the interview and collecting biological samples. Details of the study are published elsewhere(Reference Gao, Jin and Hall6). The study was approved by the Indiana University Institutional Review Board and the Institute for Environmental Health and Related Safety, Chinese Center for Disease Control and Prevention.

Information collected during the interview include age, gender, whether the participant attended school, alcohol consumption and smoking history, history of cancer, Parkinson’s disease, diabetes, hypertension, stroke, heart attack, head injury and bone fracture. Participants’ height, weight and blood pressure (two times) were also measured during the interview. BMI was derived from height and weight measurements. The average of the two blood pressure measures was used in our analyses.

Se measures

Nail samples from all study subjects were collected at the time of interview and stored in clean plastic bags labelled with subject identification numbers. The method of fluorometric determination of trace amounts of Se with 2,3-diaminonaphthalene, described in detail elsewhere(Reference Li, Cao and Sun10), was used to determine trace amounts of Se in the nail samples. Details on quality control measures implemented for the study have also been described previously(Reference Gao, Jin and Hall6).

apoE genotype

Blood spots on filter paper were collected from all study participants at the end of the interview. apoE genotype was determined by eluting DNA from a dried blood spot(Reference Yang, Hendrie, Hall, Oluwole, Hodes and Sahota11) followed by Hhal digestion of amplified products(Reference Hixson and Vernier12).

FFQ

An FFQ was administered asking participants their average daily intake of various grains, vegetables, meat, seafood, fruit, nuts, cooking oil, tea and water. The questionnaire had been developed and validated for use in Chinese populations(Reference Chen, Campbell, Li and Peto13Reference Zhai, Popkin, Ma, Yu, Guo, Jin and Ge15). Food samples were collected from various locations in each village and analysed using the same method as for the nail samples, thus providing Se measures in each food item for each village. Estimated daily Se intake was derived from the FFQ using Se levels analysed from food samples in the village in which the participants resided(Reference Cao, Yan and Zhang16, Reference He17).

Statistical analysis

Univariate associations between demographic, lifestyle and medical history variables and Se measured in nail samples were examined using mixed-effect models with Se level as the dependent variable and each village as the random effect, which controls for the potential confounding effect from correlations in Se measures obtained from participants residing in the same village. Comparisons of demographic, lifestyle and medical characteristics between apoE ε4 allele carriers and non-carriers were conducted using t tests for continuous variables and Fisher’s exact tests for categorical variables. All variables that were either univariately associated with Se levels or associated with apoE status at the P < 0·10 level were included in a multivariate mixed-effect model with Se level as the dependent variable and village as the random effect to control for potential within-village correlation. A final multivariate model was identified including those predictors significant at the 0·05 level. A separate mixed-effect model using estimated Se dietary intake as dependent variable was also conducted to examine the association of apoE status with Se dietary intake. To facilitate interpretation of parameter estimates from all mixed-effect models, we standardized all continuous variables in all models. To ensure that the association between apoE status and Se level was not due to existing CVD and potential treatments, we repeated the mixed-effect model by excluding those subjects with histories of heart attack and stroke. We also repeated the same mixed-effect models in male and female participants separately.

Results

Univariate mixed-effect models with Se levels measured in nail samples as dependent variable revealed that female participants, those who had attended school, abstainers from alcohol, non-current smokers, those with a history of stroke and those with a history of fracture appeared to have higher Se levels at the P < 0·10 level.

We compared demographic, lifestyle and medical history factors by apoE ε4 allele status (Table 1). Diastolic blood pressure was significantly higher in the ε4 carriers than in the non-carriers (P = 0·0368). Non-carriers had a significantly higher rate of fracture than ε4 carriers (2·88 % v. 0·91 %, P = 0·0353). Two other factors meeting inclusion criteria for the multivariate model were alcohol consumption (P = 0·0687) and history of head injury (P = 0·0906).

Table 1 Comparisons of demographic, lifestyle and medical history variables between carriers and non-carriers of the apoE ε4 allele: rural elderly (65 years and over) residents from Sichuan Province and Shandong Province, China (n 2000)

In Table 2, all variables significant at P = 0·10 from all univariate analyses are included in a multivariate mixed-effect model to identify significant predictors of Se levels measured in nail samples. In addition, we included BMI tertile as an additional predictor in the model because it had borderline significance for Se level just below our cut-off point of P = 0·10 (P = 0·1085) and it allowed us to control for the potential effect from body composition. A separate mixed-effect model with estimated dietary Se intake as the dependent variable is also included in Table 2. apoE ε4 carriers were shown to have significantly lower Se levels measured in nail samples, but they were not significantly different from non-carriers on estimated Se dietary intake (P = 0·6451). Final multivariate models, using nail Se levels and including only factors significant at the 0·05 level, are presented in Table 3. Controlling for gender, smoking status, history of stroke and estimated dietary Se intake, apoE ε4 carriers had significantly lower Se levels measured in nail samples than non-carriers (P = 0·0396). The results of the final model demonstrate that given the same Se dietary intake level, the apoE ε4 carriers had lower Se levels in their biological samples, equivalent to being two standard deviations lower on Se dietary intake. We also fitted the same model on a sub-sample of participants without a history of heart attack or stroke; the difference in Se level between the two genotype groups remained (P = 0·0512).

Table 2 Multivariate mixed-effect model to identify variables associated with selenium levels measured in nail samples (μg/g) and with estimated selenium dietary intake: rural elderly (65 years and over) residents from Sichuan Province and Shandong Province, China (n 2000). Village was included as a random effect to control for potential within-village correlation

Table 3 Final multivariate mixed-effect models including significant variables associated with selenium levels in nail samples (μg/g, standardized) in the entire sample and in a sub-sample of participants without history of heart attack or stroke: rural elderly (65 years and over) residents from Sichuan Province and Shandong Province, China (n 2000)

We also fitted the model in Table 3 to male and female participants separately; the results are presented in Table 4. Interestingly, dietary Se intake, while significantly related to nail Se levels in males, was not associated with nail Se levels in females. apoE ε4 carriers had lower Se levels in their nail samples for both male and female participants. The differences between apoE ε4 carriers and non-carriers were similar between males and females (0·0734 and 0·0755 standard deviations, respectively), although neither reached significance due to the reduced sample sizes from the model for the entire sample.

Table 4 Multivariate mixed-effect models including significant variables associated with selenium levels in nail samples (μg/g, standardized) in male and female participants separately: rural elderly (65 years and over) residents from Sichuan Province and Shandong Province, China (n 2000)

Discussion

In this rural elderly Chinese cohort, we found that apoE ε4 carriers had significantly lower Se levels measured in nail samples than non-carriers after adjusting for other significant covariates and controlling for estimated dietary Se intake. The difference between the two genotype groups persisted at a similar magnitude when we repeated the analysis excluding participants with histories of heart attack and stroke.

Predictors of Se levels measured in the blood, toenails or diet have been described previously(Reference Niskar, Paschal, Kieszak, Flegal, Bowman, Gunter, Pirkle, Rubin, Sampson and McGeehin3, Reference Vogt, Ziegler, Patterson and Graubard4, Reference van den Brandt, Goldbohm, van’t Veer, Bode, Hermus and Sturmans18Reference Virtanen, van’t Veer, Kok, Kardinaal and Aro20). However, most of these studies focused on demographic variables. Our results identifying smoking and male gender as factors associated with lower Se levels are consistent with previous studies(Reference Hunter, Morris, Chute, Kushner, Colditz, Stampfer, Speizer and Willett19, Reference Virtanen, van’t Veer, Kok, Kardinaal and Aro20). However, previous results on the association between increasing age and decreasing levels of Se were inconsistent(Reference Hunter, Morris, Chute, Kushner, Colditz, Stampfer, Speizer and Willett19, Reference Akbaraly, Hininger-Favier, Carriere, Arnaud, Gourlet, Roussel and Berr21), perhaps due to differences in age range in each study population. In the present cohort of participants aged 65 years and older, we did not find a significant association between age and nail Se levels. Nor did we find a significant association between alcohol consumption and Se level in this cohort, consistent with findings in previous studies(Reference van den Brandt, Goldbohm, van’t Veer, Bode, Hermus and Sturmans18Reference Virtanen, van’t Veer, Kok, Kardinaal and Aro20).

To our knowledge, the present study is the first to examine the association between apoE genotype and Se levels in a large cohort of elderly participants. The apoE gene has been shown to play a central role in cholesterol uptake and lipid metabolism and the ε4 allele is linked to increased risk of Alzheimer’s disease and CVD. The mechanism underlying the association between the apoE ε4 allele and Se levels is unclear, however. It is has been reported that apoE ε2 and apoE ε3 are more effective in maintaining neuronal health than is apoE ε4 (Reference Mahley22Reference Weisgraber and Mahley24). It is possible that apoE ε4 carriers have increased levels of oxidative stress, ischaemia and inflammation and that the increased oxidative stress in turn reduces the pool of Se.

The Framingham Offspring Study proposed that apoE ε4 may be associated with reduced antioxidant capacity based on the interaction between smoking and apoE on cardiovascular risk(Reference Talmud, Stephens, Hawe, Demissie, Cupples, Hurel, Humphries and Ordovas25). This mechanism is supported by in vitro results showing that protection of recombinant apoE against oxidation is greater in ε4 non-carriers than in ε4 carriers(Reference Smith, Miyata, Poulin, Neveux and Craig26Reference Miyata and Smith28). Results from animal studies indicate that apoE deficiency is associated with increased oxidative damage(Reference Shea, Rogers, Ashline, Ortiz and Sheu29). However, Se levels were not directly measured in these studies.

Another potential mechanism for the observed association between apoE genotype and Se levels is through reduced lipid metabolism in the ε4 carriers. Animal experiments have demonstrated that Se deficiency can lead to increased levels of plasma cholesterol, apoE and oxidized LDL in rats and mice(Reference Rosenblat and Aviram30, Reference Mazur, Nassir, Gueux, Moundras, Bellanger, Grolier, Rock and Rayssiguier31). Oxidized LDL accumulates in atherosclerotic lesions in man(Reference Aviram, Maor, Keidar, Hayek, Oiknine, Bar-El, Adler, Kertzman and Milo32) and increased LDL susceptibility to oxidation was shown in patients with hypercholesterolaemia(Reference Lavy, Brook, Dankner, Ben Amotz and Aviram33), hypertension(Reference Keidar, Kaplan, Shapira, Brook and Aviram34) and diabetes(Reference Beaudeux, Guillausseau, Peynet, Flourie, Assayag, Tielmans, Warnet and Rousselet35).

There seems to be a correlation between Se levels and metabolism of lipids and lipoproteins. Lipid metabolism may be affected by the oxidative state of the lipid molecule, on which Se would have a direct effect. A Finnish population with a higher proportion of apoE ε4 homozygous carriers and high serum cholesterol was associated with lower CHD mortality than in other communities. The lower mortality was attributed to higher antioxidant status, in particular Se intake in this population(Reference Luoma, Nayha, Sikkila and Hassi36). An interactive relationship between Se, lipids and the apoE genotype may also be worth investigating.

Our result, showing that participants with a history of stroke had increased Se levels, was surprising given the previous report on the protective effects of Se on CHD. A few studies have reported lower Se levels in acute stroke patients compared with healthy controls(Reference Zimmermann, Winnefeld, Streck, Roskos and Haberl37), although others found no significant difference(Reference Chang, Lai, Cheng, Lau and Hu38). However, in one study, lower Se was found to be associated with stroke mortality, suggesting a potential explanation that the effects of Se on CHD in relation to mortality might leave fewer participants living with stroke(Reference Virtamo, Valkeila, Alfthan, Punsar, Huttunen and Karvonen39). This possibility will be examined further in our planned follow-up of this cohort.

The strength of the present study includes the extended range of Se distribution in the cohort, allowing the exploration of other factors, and the large cohort size for the investigation. An additional strength is that we also collected dietary data, so that the association between apoE ε4 and Se could be examined controlling for dietary Se intake.

A limitation of the study is that the association between the apoE ε4 allele and Se levels is found in an elderly Chinese population, which may limit the generalizability of the findings. Independent confirmation in other populations is needed. The study also lacked cholesterol and other lipid measures in the cohort, so that it is not possible to examine any potential interactive role played by the metabolism of lipids and lipoproteins.

Acknowledgements

The research was supported by NIH grants R01 AG019181, R01 AG09956 and P30 AG10133. None of the authors has any conflicts of interest. The authors contributed as follows. Conception and design: S.G., Y.J., K.S.H., C.L., F.W.U., J.R.M. and H.C.H. Acquisition of data: S.G., Y.J., K.S.H., C.L., F.W.U., J.R.M., F.M., J.M., Y.C., J.-C.B., P.L. and H.C.H. Analysis and interpretation of data: S.G., H.C.H. and J.-Z.S. Drafting of manuscript: S.G., Y.J., C.L. and H.C.H. Critical revision of manuscript for important intellectual content: S.G., Y.J., K.S.H., C.L., F.W.U., J.R.M., F.M., J.-Z.S., J.M., Y.C., J.-C.B., P.L. and H.C.H. Statistical expertise: S.G. and J.-Z.S. Obtaining funding: S.G., Y.J., K.S.H., C.L., F.W.U., J.R.M. and H.C.H. Administrative, technical or material support: Y.J., C.L., F.M., Y.C., P.L., J.-C.B. and J.M. Supervision: S.G., Y.J., C.L. and H.C.H. We thank Dr Linda Williams for helpful comments on results reported in this manuscript.

References

1.Flatt, A, Pearce, N, Thomson, CD, Sears, MR, Robinson, MF & Beasley, R (1990) Reduced selenium in asthmatic subjects in New Zealand. Thorax 45, 9599.CrossRefGoogle ScholarPubMed
2.Rayman, MP (2000) The importance of selenium to human health. Lancet 356, 233241.CrossRefGoogle ScholarPubMed
3.Niskar, AS, Paschal, DC, Kieszak, SM, Flegal, KM, Bowman, B, Gunter, EW, Pirkle, JL, Rubin, C, Sampson, EJ & McGeehin, M (2003) Serum selenium levels in the US population: Third National Health and Nutrition Examination Survey, 1988–1994. Biol Trace Elem Res 91, 110.CrossRefGoogle ScholarPubMed
4.Vogt, TM, Ziegler, RG, Patterson, BH & Graubard, BI (2007) Racial differences in serum selenium concentration: analysis of US population data from the Third National Health and Nutrition Examination Survey. Am J Epidemiol 166, 280288.CrossRefGoogle ScholarPubMed
5.World Health Organization (1987) Selenium. A Report of the International Programme on Chemical Safety. Environmental Health Criteria Series no. 58. Geneva: WHO.Google Scholar
6.Gao, S, Jin, Y, Hall, KS et al. (2007) Selenium level and cognitive function in rural elderly Chinese. Am J Epidemiol 165, 955965.CrossRefGoogle ScholarPubMed
7.Stone, WL, Stewart, ME, Nicholas, C & Pavuluri, S (1986) Effects of dietary selenium and vitamin E on plasma lipoprotein cholesterol levels in male rats. Ann Nutr Metab 30, 94103.CrossRefGoogle ScholarPubMed
8.Stone, WL, Scott, RL, Stewart, EM & Kheshti, A (1994) Lipoprotein alterations in the spontaneously hypertensive rat fed diets deficient in selenium and vitamin E. Proc Soc Exp Biol Med 206, 130137.CrossRefGoogle ScholarPubMed
9.Sengupta, A, Carlson, BA, Hoffmann, VJ, Gladyshev, VN & Hatfield, DL (2008) Loss of housekeeping selenoprotein expression in mouse liver modulates lipoprotein metabolism. Biochem Biophys Res Commun 365, 446452.CrossRefGoogle ScholarPubMed
10.Li, M, Cao, J & Sun, S (1991) Micro-fluorometric determination of trace amount of selenium in blood, hair and milk powder. Chinese J Public Health 10, 306308.Google Scholar
11.Yang, M, Hendrie, HC, Hall, KS, Oluwole, OS, Hodes, ME & Sahota, A (1996) Improved procedure for eluting DNA from dried blood spots. Clin Chem 42, 11151116.Google ScholarPubMed
12.Hixson, JE & Vernier, DT (1990) Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 31, 545548.Google ScholarPubMed
13.Chen, J, Campbell, TC, Li, J & Peto, R (1990) Diet, Lifestyle and Mortality in China. Oxford/Ithaca, NY/Beijing: Oxford University Press/Cornell University Press/People’s Publishing House.Google Scholar
14.Cao, J, Chen, S & Sun, S (1993) A comparison of methods for estimating large population dietary fluoride intake in coal burning high fluoride communities. J Hyg Res 22, 5254.Google Scholar
15.Zhai, F, Popkin, BM, Ma, L, Yu, W, Guo, X, Jin, S & Ge, K (1996) The evaluation of 24-hour individual dietary recall method in China. J Hyg Res 25, 5156.Google Scholar
16.Cao, J, Yan, B & Zhang, S (1996) Relations between heavy exposure of selenium-fluoride and human health. J Hyg Res 25, 287290.Google Scholar
17.He, L (2003) Summary for method and application of food frequency survey. J Foreign Med Sci: Hyg Sect 30, 368371.Google Scholar
18.van den Brandt, PA, Goldbohm, RA, van’t Veer, P, Bode, P, Hermus, RJ & Sturmans, F (1993) Predictors of toenail selenium levels in men and women. Cancer Epidemiol Biomarkers Prev 2, 107112.Google ScholarPubMed
19.Hunter, DJ, Morris, JS, Chute, CG, Kushner, E, Colditz, GA, Stampfer, MJ, Speizer, FE & Willett, WC (1990) Predictors of selenium concentration in human toenails. Am J Epidemiol 132, 114122.CrossRefGoogle ScholarPubMed
20.Virtanen, SM, van’t Veer, P, Kok, F, Kardinaal, AF & Aro, A (1996) Predictors of adipose tissue tocopherol and toenail selenium levels in nine countries: the EURAMIC study. European Multicentre Case–Control Study on Antioxidants, Myocardial Infarction, and Cancer of the Breast. Eur J Clin Nutr 50, 599606.Google ScholarPubMed
21.Akbaraly, NT, Hininger-Favier, I, Carriere, I, Arnaud, J, Gourlet, V, Roussel, AM & Berr, C (2007) Plasma selenium over time and cognitive decline in the elderly. Epidemiology 18, 5258.CrossRefGoogle ScholarPubMed
22.Mahley, RW (1988) Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 240, 622630.CrossRefGoogle ScholarPubMed
23.Mahley, RW & Rall, SC Jr (2000) Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet 1, 507537.CrossRefGoogle ScholarPubMed
24.Weisgraber, KH & Mahley, RW (1996) Human apolipoprotein E: the Alzheimer’s disease connection. FASEB J 10, 14851494.CrossRefGoogle ScholarPubMed
25.Talmud, PJ, Stephens, JW, Hawe, E, Demissie, S, Cupples, LA, Hurel, SJ, Humphries, SE & Ordovas, JM (2005) The significant increase in cardiovascular disease risk in APOEε4 carriers is evident only in men who smoke: potential relationship between reduced antioxidant status and ApoE4. Ann Hum Genet 69, 613622.CrossRefGoogle ScholarPubMed
26.Smith, JD, Miyata, M, Poulin, SE, Neveux, LM & Craig, WY (1998) The relationship between apolipoprotein E and serum oxidation-related variables is apolipoprotein E phenotype dependent. Int J Clin Lab Res 28, 116121.CrossRefGoogle ScholarPubMed
27.Jolivalt, C, Leininger-Muller, B, Bertrand, P, Herber, R, Christen, Y & Siest, G (2000) Differential oxidation of apolipoprotein E isoforms and interaction with phospholipids. Free Radic Biol Med 28, 129140.CrossRefGoogle ScholarPubMed
28.Miyata, M & Smith, JD (1996) Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and β-amyloid peptides. Nat Genet 14, 5561.CrossRefGoogle ScholarPubMed
29.Shea, TB, Rogers, E, Ashline, D, Ortiz, D & Sheu, MS (2002) Apolipoprotein E deficiency promotes increased oxidative stress and compensatory increases in antioxidants in brain tissue. Free Radic Biol Med 33, 11151120.CrossRefGoogle ScholarPubMed
30.Rosenblat, M & Aviram, M (1998) Macrophage glutathione content and glutathione peroxidase activity are inversely related to cell-mediated oxidation of LDL: in vitro and in vivo studies. Free Radic Biol Med 24, 305317.CrossRefGoogle ScholarPubMed
31.Mazur, A, Nassir, F, Gueux, E, Moundras, C, Bellanger, J, Grolier, P, Rock, E & Rayssiguier, Y (1996) Diets deficient in selenium and vitamin E affect plasma lipoprotein and apolipoprotein concentrations in the rat. Br J Nutr 76, 899907.CrossRefGoogle ScholarPubMed
32.Aviram, M, Maor, I, Keidar, S, Hayek, T, Oiknine, J, Bar-El, Y, Adler, Z, Kertzman, V & Milo, S (1995) Lesioned low density lipoprotein in atherosclerotic apolipoprotein E-deficient transgenic mice and in humans is oxidized and aggregated. Biochem Biophys Res Commun 216, 501513.CrossRefGoogle ScholarPubMed
33.Lavy, A, Brook, GJ, Dankner, G, Ben Amotz, A & Aviram, M (1991) Enhanced in vitro oxidation of plasma lipoproteins derived from hypercholesterolemic patients. Metabolism 40, 794799.CrossRefGoogle ScholarPubMed
34.Keidar, S, Kaplan, M, Shapira, C, Brook, JG & Aviram, M (1994) Low density lipoprotein isolated from patients with essential hypertension exhibits increased propensity for oxidation and enhanced uptake by macrophages: a possible role for angiotensin II. Atherosclerosis 107, 7184.CrossRefGoogle ScholarPubMed
35.Beaudeux, JL, Guillausseau, PJ, Peynet, J, Flourie, F, Assayag, M, Tielmans, D, Warnet, A & Rousselet, F (1995) Enhanced susceptibility of low-density lipoprotein to in vitro oxidation in type 1 and type 2 diabetic patients. Clin Chim Acta 239, 131141.CrossRefGoogle ScholarPubMed
36.Luoma, PV, Nayha, S, Sikkila, K & Hassi, J (1995) High serum α-tocopherol, albumin, selenium and cholesterol, and low mortality from coronary heart disease in northern Finland. J Intern Med 237, 4954.CrossRefGoogle ScholarPubMed
37.Zimmermann, C, Winnefeld, K, Streck, S, Roskos, M & Haberl, RL (2004) Antioxidant status in acute stroke patients and patients at stroke risk. Eur Neurol 51, 157161.CrossRefGoogle ScholarPubMed
38.Chang, CY, Lai, YC, Cheng, TJ, Lau, MT & Hu, ML (1998) Plasma levels of antioxidant vitamins, selenium, total sulfhydryl groups and oxidative products in ischemic-stroke patients as compared to matched controls in Taiwan. Free Radic Res 28, 1524.CrossRefGoogle ScholarPubMed
39.Virtamo, J, Valkeila, E, Alfthan, G, Punsar, S, Huttunen, JK & Karvonen, MJ (1985) Serum selenium and the risk of coronary heart disease and stroke. Am J Epidemiol 122, 276282.CrossRefGoogle ScholarPubMed
You have Access

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Selenium level is associated with apoE ε4 in rural elderly Chinese
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

Selenium level is associated with apoE ε4 in rural elderly Chinese
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

Selenium level is associated with apoE ε4 in rural elderly Chinese
Available formats
×
×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *