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Meta-Analysis on the Association Between the TF Gene rs1049296 and AD

Published online by Cambridge University Press:  23 September 2014

Yun Wang
Affiliation:
Department of Neurology, The Second Hospital of Shandong University, Jinan, PR China
Shunliang Xu
Affiliation:
Department of Neurology, The Second Hospital of Shandong University, Jinan, PR China
Zhen Liu
Affiliation:
Department of Neurology, The Second Hospital of Shandong University, Jinan, PR China
Chao Lai
Affiliation:
Department of Neurology, The Second Hospital of Shandong University, Jinan, PR China
Zhaohong Xie
Affiliation:
Department of Neurology, The Second Hospital of Shandong University, Jinan, PR China
Cuiping Zhao
Affiliation:
Department of Neurology, The Second Hospital of Shandong University, Jinan, PR China
Yan Wei
Affiliation:
Department of Neurology, The Second Hospital of Shandong University, Jinan, PR China
Jian Zhong Bi
Affiliation:
Department of Neurology, The Second Hospital of Shandong University, Jinan, PR China
Corresponding
E-mail address:
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Abstract:

Background:

Polymorphisms of genes participating in iron transportation have been associated with Alzheimer's disease (AD) risk. The association between transferrin (TF) gene rs1049296 (P570S) polymorphism and AD is controversial.

Methods:

We performed meta analysis on data from 19 studies with 6310 cases and 13661 controls to reexamine the association between the TF gene rs1049296 polymorphism and AD. We applied a fixed-effects model to combine the odds ratio (OR) and 95% confidence intervals (95% CI). Egger's test was carried out to evaluate the potential publication bias.

Results:

The overall ORs with 95% CIs showed statistical association between the TF gene rs1049296 polymorphism and the risk of AD in the allele contrast, the recessive model and the dominant model for allele C2 (fixed-effects pooled OR 1.11; 95% CI 1.05 to 1.17, pooled OR 1.13; 95% CI 1.06 to 1.21, and pooled OR 1.23; 95% CI 1.03 to 1.47, respectively). In the contrast of C2C2+C2C1 vs C1C1, large heterogeneity among the Asian subgroup (p=0.041, I2= 68.6%) was observed but not among the overall population (p = 0.184, I2= 22.4%). No publication bias was observed.

Conclusions:

The present meta analysis demonstrated that TF gene rs1049296 polymorphism is a genetic determinant of AD.

Type
Original Article
Copyright
Copyright © The Canadian Journal of Neurological 2013

References

1.Bertram, L, Tanzi, RE.The current status of Alzheimer's disease genetics: What do we tell the patients? Pharmacol Res. 2004;50:385–96.CrossRefGoogle Scholar
2.Strittmatter, WJ, Saunders, AM, Schmechel, D, et al.Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA. 1993;90:197781.CrossRefGoogle ScholarPubMed
3.Daw, EW, Payami, H, Nemens, EJ, et al.The number of trait loci in late-onset Alzheimer disease. Am J Hum Genet. 2000;66:196204.CrossRefGoogle ScholarPubMed
4.Connor, JR, Menzies, SL, St Martin, SM, Mufson, EJ.A histochemical study of iron, transferrin, and ferritin in Alzheimer's disease brains. J Neurosci Res. 1992;31:7583.CrossRefGoogle Scholar
5.Van Rensburg, SJ, Carstens, ME, Potocnik, FC, et al.Transferrin C2 and Alzheimer's disease: another piece of the puzzle found? Med Hypotheses. 1995;44:268–72.CrossRefGoogle Scholar
6.Ding, B, Chen, KM, Ling, HW, et al.Correlation of iron in the hippocampus with MMSE in patients with Alzheimer's disease. J Magn Reson Imaging. 2009;29:7938.CrossRefGoogle Scholar
7.Jiang, D, Li, X, Williams, R, et al.Ternary complexes of iron, amyloid-beta, and nitrilotriacetic acid: binding affinities, redox properties, and relevance to iron-induced oxidative stress in Alzheimer's disease. Biochemistry. 2009;48:793947.CrossRefGoogle Scholar
8.van Rensburg, SJ, Carstens, ME, Potocnik, FC, Aucamp, AK, Taljaard, JJ.Increased frequency of the transferrin C2 subtype in Alzheimer's disease. Neuroreport. 1993;4:126971.CrossRefGoogle ScholarPubMed
9.Lehmann, DJ, Schuur, M, Warden, DR, et al.Transferrin and HFE genes interact in Alzheimer's disease risk: the Epistasis Project. Neurobiol Aging. 2012;33:202.e1-13.CrossRefGoogle Scholar
10.Giambattistelli, F, Bucossi, S, Salustri, C, et al.Effects of hemochromatosis and transferring gene mutations on iron dyshomeostasis, liver dysfunction and on the risk of Alzheimer's disease. Neurobiol. 2011;33:163341.Google Scholar
11.Kauwe, JS, Bertelsen, S, Mayo, K, et al.Alzheimer's disease neuroimaging initiative. Suggestive synergy between genetic variants in TF and HFE as risk factors for Alzheimer's disease. Am J Med Genet. B Neuropsychiatr. Genet. 2010;153b:9559.CrossRefGoogle Scholar
12.Laumet, G, Chouraki, V, Grenier-Boley, B, et al.Systematic analysis of candidate genes for Alzheimer's disease in a French, genome-wide association study. J Alzheimers Dis. 2010;20:11818.CrossRefGoogle Scholar
13.Giedraitis, V, Kilander, L, Degerman-Gunnarsson, M, et al.Genetic analysis of Alzheimer's disease in the Uppsala Longitudinal Study of Adult Men. Dement geriatr Cogn Disord. 2009;27:5968.CrossRefGoogle ScholarPubMed
14.Li, H, Wetten, S, Li, L, et al.Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease. Arch Neurol. 2008;65:4553.CrossRefGoogle ScholarPubMed
15.Reiman, EM, Webster, JA, Myers, AJ, et al.GAB2 alleles modify Alzheimer's risk in APOE epsilon4 carriers. Neuron. 2007;54:713–20.CrossRefGoogle ScholarPubMed
16.Blázquez, L, De Juan, D, Ruiz-Martínez, J, et al.Genes related to iron metabolism and susceptibility to Alzheimer's disease in Basque population. Neurobiol Aging. 2007;28:19413.CrossRefGoogle Scholar
17.Rondeau, V, Iron, A, Letenneur, L, et al.Analysis of the effect of aluminum in drinking water and transferrin C2 allele on Alzheimer's disease. Eur J Neurol. 2006;13:10225.CrossRefGoogle Scholar
18.Robson, KJ, Lehmann, DJ, Wimhurst, VL, et al.Synergy between the C2 allele of transferrin and the C282Y allele of the haemochromatosis gene (HFE) as risk factors for developing Alzheimer's disease. J Med Genet. 2004;41:2615.CrossRefGoogle ScholarPubMed
19.Corder, EH, Beaumont, H.Susceptibility groups for Alzheimer's disease (OPTIMA cohort): integration of gene variants and biochemical factors. Mech Ageing Dev. 2007;128:7682.CrossRefGoogle Scholar
20.Lehmann, DJ, Worwood, M, Ellis, R, et al.Iron genes, iron load and risk of Alzheimer's disease. J Med Genet. 2006;43:e52.CrossRefGoogle ScholarPubMed
21.Zambenedetti, P, De Bellis, G, Biunno, I, Musicco, M, Zatta, P.Transferrin C2 variant does confer a risk for Alzheimer's disease in caucasians. J Alzheimers Dis. 2003;5:4237.CrossRefGoogle Scholar
22.Lleó, A, Blesa, R, Angelopoulos, C, et al.Transferrin C2 allele, haemochromatosis gene mutations, and risk for Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2002;72:8201.CrossRefGoogle ScholarPubMed
23.Hussain, RI, Ballard, CG, Edwardson, JA, Morris, CM.Transferrin gene polymorphism in Alzheimer's disease and dementia with Lewy bodies in humans. Neurosci Lett. 2002;17:1316.CrossRefGoogle Scholar
24.Emahazion, T, Feuk, L, Jobs, M, et al.SNP association studies in Alzheimer's disease highlight problems for complex disease analysis. Trends Genet. 2001;17:407–13.CrossRefGoogle Scholar
25.Van Landeghem, GF, Sikström, C, Beckman, LE, Adolfsson, R, Beckman, L.Transferrin C2, metal binding and Alzheimer's disease. Neuroreport. 1998;9:1779.CrossRefGoogle Scholar
26.Zhang, P, Yang, Z, Zhang, C, et al.Association study between lateonset Alzheimer's disease and the transferrin gene polymorphisms in Chinese. Neurosci Lett. 2003;349:209–11.CrossRefGoogle Scholar
27.Kim, KW, Jhoo, JH, Lee, JH, et al.Transferrin C2 variant does not confer a risk for Alzheimer's disease in Koreans. Neurosci Lett. 2001;308:45–8.CrossRefGoogle ScholarPubMed
28.Kim, KW, Jhoo, JH, Lee, JH, et al.Neither the butyrylcholinesterase K variant nor transferrin C2 variant confers a risk for Alzheimer's disease in Koreans. J Neural Transm. 2001;108:115966.CrossRefGoogle ScholarPubMed
29.Namekata, K, Imagawa, M, Terashi, A, et al.Association of transferrin C2 allele with late-onset Alzheimer's disease. Hum Genet. 1997;101:1269.CrossRefGoogle ScholarPubMed
30.van Rensburg, SJ, Potocnik, FC, De Villiers, JN, Kotze, MJ, Taljaard, JJ.Earlier age of onset of Alzheimer's disease in patients with both the transferrin C2 and apolipoprotein E-epsilon 4 alleles. Ann N Y Acad Sci. 2000;903:2003.CrossRefGoogle ScholarPubMed
31.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 4th ed. Washington DC: American Psychiatric Association; 1994. p. 37–9.Google Scholar
32.McKhann, G, Drachman, D, Folstein, M, et al.Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology. 1984;34:939–44.CrossRefGoogle ScholarPubMed
33.Mirra, SS, Heyman, A, McKeel, D, et al.The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. 1991;41:479–86.CrossRefGoogle Scholar
34.Lau, J, Ioannidis, JP, Schmid, CH.Quantitative synthesis in systematic reviews. Ann Intern Med. 1997;127:8206.CrossRefGoogle ScholarPubMed
35.Higgins, JP, Thompson, SG, Deeks, JJ, Altman, DG.Measuring inconsistency in meta-analyses. Br Med J. 2003;327:557–60.CrossRefGoogle ScholarPubMed
36.Mantel, N, Haenszel, W.Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.Google Scholar
37.DerSimonian, R, Laird, N.Meta analysis in clinical trials. Control Clin Trials. 1986;7:177–88.CrossRefGoogle ScholarPubMed
38.Galbraith, RF.A note on graphical presentation of estimated odds ratios from several clinical trials. Stat Med. 1988;7:889–94.CrossRefGoogle ScholarPubMed
39.Egger, M, Davey Smith, G, Schneider, M, Minder, C.Bias in meta analysis detected by a simple, graphical test. Br Med J. 1997;315: 629–34.CrossRefGoogle Scholar
40.Shi, H, Belbin, O, Medway, C, et al.Genetic variants influencing human aging from late-onset Alzheimer's disease (LOAD) genome-wide association studies (GWAS). Neurobiol Aging. 2012;33:1849.e5-18.CrossRefGoogle Scholar
41.Butterfield, DA.Amyloid beta-peptide (1-42)-induced oxidative stress and neurotoxicity: implications for neurodegeneration in Alzheimer's disease brain. A review. Free Radic Res. 2002;36:130713.CrossRefGoogle ScholarPubMed
42.Venkateshappa, C, Harish, G, Mahadevan, A, et al.Elevated oxidative stress and decreased antioxidant function in the human hippocampus and frontal cortex with increasing age: implications for neurodegeneration in Alzheimer's disease. Neurochem Res. 2012;37:160114.CrossRefGoogle ScholarPubMed
43.Bush, AI, Tanzi, RE.Therapeutics for Alzheimer's disease based on the metal hypothesis. Neurotherapeutics. 2008;5:421–32.CrossRefGoogle ScholarPubMed
44.Horowitz, MP, Greenamyre, JT.Mitochondrial iron metabolism and its role in neurodegeneration. J Alzheimers Dis. 2010;20 Suppl 2:S55168.CrossRefGoogle Scholar
45.Smith, MA, Zhu, X, Tabaton, M, et al.Increased iron and free radical generation in preclinical Alzheimer disease and mild cognitive impairment. J Alzheimers Dis. 2010;19:363–72.CrossRefGoogle ScholarPubMed
46.Macedo, MF, de Sousa, M.Transferrin and the transferrin receptor: of magic bullets and other concerns. Inflamm Allergy Drug Targets. 2008;7:4152.CrossRefGoogle ScholarPubMed
47.Bertram, L, McQueen, MB, Mullin, K, Blacker, D, Tanzi, RE.Systematic meta-analyses of Alzheimer disease genetic association studies: the Alzgene database. Nat genet. 2007;39:1723.CrossRefGoogle ScholarPubMed
48.Schjeide, BM, McQueen, MB, Mullin, K, et al.Assessment of Alzheimer's disease case-control associations using family-based methods. Neurogenetics. 2009;10:1925.CrossRefGoogle ScholarPubMed

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