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This work aims to examine the interaction between apo A2 (Apo A-II) –265T > C SNP and dietary total antioxidant capacity (DTAC) on inflammation and oxidative stress in patients with type 2 diabetes mellitus. The present cross-sectional study included 180 patients (35–65 years) with identified Apo A-II genotype. Dietary intakes were assessed by a FFQ. DTAC was computed using the international databases. IL-18 (IL18), high-sensitivity C-reactive protein (hs-CRP), pentraxin (PTX3), serum total antioxidant capacity (TAC), superoxide dismutase (SOD) activity and 8-isoprostaneF2α (PGF2α) markers were obtained according to standard protocols. General linear model was used to evaluate the interaction. The interaction of gene and DTAC (PFRAP = 0·039 and PORAC = 0·042) on PGF2α level was significant after adjusting for confounders. A significant interaction was observed on IL18 level (PORAC = 0·018 and PFRAP = 0·048) and SOD (PTEAC = 0·037) in obese patients. Among patients whose DTAC was higher than the median intake, the levels of hs-CRP and PGF2α were significantly higher only in individuals with CC genotype. Serum TAC (PFRAP = 0·030, PORAC = 0·049) and SOD were significantly lower in the CC genotype. There was a favourable relationship between the high-DTAC and SOD (obese: PTEAC = 0·034, non-obese: PFRAP = 0·001, PTRAP < 0·0001, PTEAC = 0·003 and PORAC = 0·001) and PGF2α (non-obese: PORAC = 0·024) in T-allele carriers. The rs5082 SNP interacts with DTAC to influence several cardiometabolic risk factors. Also, we found dietary recommendations for antioxidant-rich foods intake might be useful in the prevention of diabetes complications in the T carrier more effectively than the CC genotype. Future large studies are required to confirm these results.
Branched-chain amino acids (BCAA) are considered markers of insulin resistance (IR) in subjects with obesity. In this study, we evaluated whether the presence of the SNP of the branched-chain aminotransferase 2 (BCAT2) gene can modify the effect of a dietary intervention (DI) on the plasma concentration of BCAA in subjects with obesity and IR. A prospective cohort study of adult subjects with obesity, BMI ≥ 30 kg/m2, homeostatic model assessment-insulin resistance (HOMA-IR ≥ 2·5) no diagnosed chronic disease, underwent a DI with an energy restriction of 3140 kJ/d and nutritional education for 1 month. Anthropometric measurements, body composition, blood pressure, resting energy expenditure, oral glucose tolerance test results, serum biochemical parameters and the plasma amino acid profile were evaluated before and after the DI. SNP were assessed by the TaqMan SNP genotyping assay. A total of eighty-two subjects were included, and fifteen subjects with a BCAT2 SNP had a greater reduction in leucine, isoleucine, valine and the sum of BCAA. Those subjects also had a greater reduction in skeletal muscle mass, fat-free mass, total body water, blood pressure, muscle strength and biochemical parameters after 1 month of the DI and adjusting for age and sex. This study demonstrated that the presence of the BCAT2 SNP promotes a greater reduction in plasma BCAA concentration after adjusting for age and sex, in subjects with obesity and IR after a 1-month energy-restricted DI.
Several investigations revealed the association between ApoA2 concentration and lipid profile, inflammation and oxidative stress markers. Dietary habits also play a major role in the health status of individuals with type 2 diabetes mellitus (T2DM). This study aimed to investigate the interaction of ApoA2–256T > C with dietary indexes on ghrelin and leptin hormones together with biochemical markers among individuals with T2DM. A cross-sectional study was conducted on 726 randomly selected individuals with T2DM. A validated FFQ was used to evaluate Healthy Eating Index, Dietary Quality Index-International (DQI-I) and Dietary Phytochemical Index (DPI). ApoA2–256T > C genotypes were detected by real-time-PCR. Ghrelin, leptin and biochemical markers were also assessed. ANCOVA was used for the interaction between the polymorphism and dietary indexes. A significant interaction was observed between ApoA2–256T > C and DQI-I on high-sensitivity C-reactive protein (hs-CRP) level and superoxide dismutase (SOD) activity. Besides, the interaction of the SNP and DPI significantly affected hs-CRP and 8-isoprostane F2α (PGF2α) levels. CC in the second tertile of DPI had the lowest hs-CRP level, and it was elevated due to adhering to DQI-I (Pinteraction = 0·01 and 0·04, respectively). Moreover, T-allele (protective allele) carriers with the highest level of PGF2α and SOD activity were those in the second tertile of DPI and DQI-I, respectively (Pinteraction = 0·03 and 0·007, respectively). SOD activity, hs-CRP and PGF2α concentration may be modified in T-allele carriers and CC by the adherence to DPI and DQI-I, though additional studies are required to confirm these findings.
Khasi mandarin (Citrus reticulata Blanco) is a commercial mandarin variety grown in northeast India and one of the 175 Indian food items included in the global first food atlas. The cultivated plantations of Khasi mandarin grown prominently in the lower Brahmaputra valley of Assam, northeast India, have been genetically eroded. The lack in the efforts for conservation of genetic variability in this mandarin variety prompted diversity analysis of Khasi mandarin germplasm across the region. Thus, the study aimed to investigate genetic diversity and partitioning of the genetic variations within and among 92 populations of Khasi mandarin collected from 10 cultivated sites in Kamrup and Kamrup (M) districts of Assam, India, using Inter-Simple Sequence Repeat (ISSR) markers. The amplification of genomic DNA with 17 ISSR primers yielded 216 scorable DNA amplicons of which 177 (81.94%) were polymorphic. The average polymorphism information content was 0.39 per primer. The total genetic diversity (HT = 0.28 ± 0.03) was close to the diversity within the population (HS = 0.20 ± 0.01). A high mean coefficient of gene differentiation (GST = 0.29) reflected a high level of gene flow (Nm = 1.22), indicating high genetic differentiation among the populations. Analysis of Molecular Variance (AMOVA) showed 78% of intra-population differentiation, 21% among the population and 1% among the districts. The obtained results indicate the existence of a high level of genetic diversity in the cultivated Khasi mandarin populations, indicating the need for preservation of each existing population to revive the dying out orchards in northeast India.
The present study aimed to investigate the interaction of Apo A-II polymorphism and dietary total antioxidant capacity (DTAC) with lipid profile and anthropometric markers in patients with type 2 diabetes (T2DM) that are at risk for atherosclerosis. This cross-sectional study was conducted on 778 patients with T2DM (35–65 years). Dietary intakes were assessed by a 147-item food frequency questionnaire. DTAC was computed using international databases. Participants were categorised into two groups based on rs5082 genotypes. The gene–diet interaction was analysed by an ANCOVA multivariate interaction model. Total cholesterol, TC; triacylglycerol, TG; high- and low-density lipoprotein, HDL and LDL; TC–HDL ratio; waist circumference, WC and body mass index, BMI were obtained according to standard protocols. Overall, the frequency of CC homozygous was 12⋅1 % among study participants. We found that a significant interaction between rs5082 variants and DTAC on mean WC (PTEAC = 0⋅044), TC concentration (PFRAP = 0⋅049 and PTEAC = 0⋅031) and TC/HDL (PFRAP = 0⋅031 and PTRAP = 0⋅040). Among patients whose DTAC was higher than the median intake, the mean of weight, WC and TC/HDL were significantly higher only in individuals with CC genotype. Also, the high DTAC was associated with a lower TC concentration only in T-allele carriers (PFRAP = 0⋅042). We found that adherence to a diet with high total antioxidant capacity can improve the complications of diabetes and atherosclerosis in the T carrier genotype more effectively than the CC genotype. These results could indicate the anti-atherogenic properties of Apo A-II. However, further studies are needed to shed light on this issue.
Some studies have suggested that the Toll-like receptor 9 polymorphism (TLR9 rs352140) is closely related to the risk of bacterial meningitis (BM), but this is subject to controversy. This study set out to estimate whether the TLR9 rs352140 polymorphism confers an increased risk of BM. Relevant literature databases were searched including PubMed, Embase, the Cochrane Library and China National Knowledge Infrastructure (CNKI) up to August 2020. Seven case-control studies from four publications were enrolled in the present meta-analysis. Odds ratios (OR) and confidence intervals (95% CI) were calculated to estimate associations between BM risk and the target polymorphism. Significant associations identified were allele contrast (A vs. G: OR 0.66, 95% CI 0.59–0.75, P = 0.000), homozygote comparison (AA vs. AG/GG: OR 0.62, 95% CI 0.49–0.78, P = 0.000), heterozygote comparison (A vs. G: OR 0.74, 95% CI 0.61–0.91, P = 0.005), recessive genetic model (AA vs. AG/GG: OR 0.78, 95% CI 0.65–0.93, P = 0.006) and dominant genetic model (AA vs. AG/GG: OR 0.70, 95% CI 0.57–0.85, P = 0.000). The findings indicate that, in contrast to some studies, the TLR9 rs352140 polymorphism is associated with a decreased risk for BM.
TLR3 and IL-10 play a crucial role in antiviral defence. However, there is a controversy between TLR3 rs3775291 and IL-10 rs1800871 polymorphisms and the risk of hepatitis B virus (HBV) infection. The purpose of this study is to explore the relationship between the two single nucleotide mutations and the risk of HBV infection by meta-analysis. Medline, EMBASE, Web of Science, CNKI, China Wanfang database were searched for the case-control studies on the relationship between TLR3 rs3775291 and IL-10 rs1800871 polymorphism and susceptibility to HBV, updated to June 2020. The data were analysed by Stata 15.0 software. A total of 22 articles were included. The results showed that in the analysis of IL10 rs1800871 polymorphism and the risk of HBV infection, the pooled OR was 1.21 (95% CI 1.06–1.37), 1.28 (95% CI 1.04–1.56) and 1.20 (95% CI 1.06–1.37) and 1.40 (95% CI 1.07–1.83) in the allele model (C vs. T), dominant model (CC+CT vs. TT), recessive model (CC vs. CT+TT) and homozygous model (CC vs. TT), respectively. There was no statistical significance in the heterozygote model. A subgroup analysis of the Asian population showed similar results. The analysis of TLR3 rs3775291 polymorphism and the risk of HBV showed that in the allele model (T vs. C), the pooled OR was 1.30 (95% CI 1.05–1.61). Except for the recessive model, no significances were found in other genetic models. In conclusion, TLR3 rs3775291 and IL-10 rs1800871 polymorphisms are associated with the risk of HBV. Allele C and genotype CC at IL10 rs1800871 loci, as well as allele T and genotype TT at TLR rs3775291 loci, may increase susceptibility to Hepatitis B infection.
Cowpea (Vigna unguiculata L. Walp.) is an important grain legume in tropical and subtropical regions. It requires low resource inputs and has a high nutritional value. Therefore, cowpea can play an important role in the development of agriculture. In southern Mexico, Mayan farmers have conserved and developed cowpea landraces for centuries. Nevertheless, information on their genetic diversity, conservation status and potential use is minimal. To generate information toward sustainable use, management and conservation of this species, we evaluated the genetic diversity and structure of 20 cowpea landraces from southeast Mexico using 10 inter-simple sequence repeat (ISSR) molecular markers. These ISSR markers generated 68 loci with a 67.7% polymorphism rate and average polymorphic information content of 0.36. The results of Bayesian assignation and the UPGMA analysis suggest the formation of two main groups defined by their genetic origin in southeast Mexico. High levels of genetic structure were found with a moderate level of genetic diversity distributed mainly between landraces. Low levels of intra-landrace variability were observed. Two landraces (P5 and P12) from Calakmul resulted in the high levels of genetic diversity. The selected markers were efficient at assessing genetic variability among Mexican cowpea landraces, providing valuable information that can be used in local conservation and participatory breeding programmes.
The A1 allele of the D2 dopamine receptor (DRD2) gene has been associated with alcohol dependence. However, the expression of this allele risk on the severity of drinking behavior in patients with alcohol dependence has not been systematically explored. The present study examines the association between DRD2 A1+(A1/A1 and A1/A2 genotypes) and A1– (A2/A2 genotype) allele status and key drinking parameters in alcohol-dependent patients. A sample of Caucasian adults was recruited from an alcohol detoxification unit. A clinical interview and the Alcohol Dependence Scale (ADS) questionnaire provided data on consumption, dependence, chronology of drinking and prior detoxification. A1+ allele compared to A1– allele patients consumed higher quantities of alcohol, commenced problem drinking at an earlier age, experienced a shorter latency between first introduction to alcohol to the onset of problem drinking and had higher ADS scores. Moreover, A1+ allele patients had more detoxification attempts than their A1– allele counterparts. In sum, alcohol-dependent patients with the DRD2 A1 allele compared to patients without this allele are characterized by greater severity of their disorder across a range of problem drinking indices. The implications of these findings are discussed.
Addiction to various substances, including drugs and alcohol, probably arises from a combination of environmental and genetic factors. The genetic vulnerability to drug addiction is supported by several familial, adoption and twin studies. However, as in other mental disorders, the genetic vulnerability to drug addiction appears complex: these disorders do not follow the rules of Mendelian inheritance. Instead, they are probably influenced by multiple susceptibility genes, each of which contributes to the disorder. The more genes necessary for a disorder, the harder it is to detect any of them. This difficulty is magnified by the role of environmental factors. Association studies using the candidate gene approach can identify susceptibility genes for drug abuse supported by the pathophysiological hypothesis of the illness. This review will focus on the clinical and molecular genetic studies in drug abuse.
We investigated the genotype frequency of methylenetetrahydrofolate reductase (MTHFR) 1298A > C polymorphism in the group of patients with bipolar disorder type I (BDI) (n = 200) and schizophrenia (n = 200) and in the control group (n = 300). Odds ratio (OR) for patients with BD and schizophrenia in 1298CC homozygous state was 3.768 (95% CI = 1.752–8.104); P = 0.0003; (P = 0.0006 after Bonferroni correction) and 2.694; (95% CI = 1.207–6.013); P = 0.0123 (P = 0.0246 after Bonferroni correction), respectively. The stratification of patients based on gender revealed significant association of 1298CC genotype with female patients only with BDI (OR = 7.293; 95% CI = 2.017–26.363; P = 0.0005).
Our results confirm association of BD and schizophrenia with the 1p36.3 MTHFR locus and with the methyl group transfer using folate-dependent one-carbon pathway.
Suicidal behavior runs in families and is prevalent in adolescence. Case-control and family-based studies in this age group failed to find a genetic association that survived replications. Gene environment approach gave new hope for possible associations especially with the short allele of the serotonin transporter promoter polymorphism (5-HTTLPR). However, a recent meta-analysis raised doubts about the consistency of these findings. Some new structural and functional imaging data may shade light on the age-related and gender-related development of the brain. This review suggests a new approach to gene by environment and timing interaction to understand the interplay that leads to suicidality in adolescents and young adults.
This study aimed to investigate the possible association between T102C and –1438 G/A polymorphism in the 5-HT2A receptor gene and susceptibility to and clinical features of obsessive–compulsive disorder (OCD).
Fifty-eight patients with OCD and 83 healthy controls were included in the study. All patients were interviewed and rated by Yale-Brown Obsessive–Compulsive Scale. T102C and –1438 G/A polymorphisms of 5-HT2A receptor gene were determined by PCR technique in DNAs of peripheral leucocytes.
OCD patients and healthy controls did not show significant differences in genotype distribution for both polymorphisms investigated. We found that frequencies of the TT genotype for T102C polymorphism and the AA genotype for –1438 G/A polymorphism were significantly higher in patients with severe OCD compared to those with moderate or moderate–severe OCD.
The –1438 G/A and T102C polymorphisms of the 5-HT2A receptor gene are not associated with an increased risk of OCD. Our data suggest that the TT genotype of T102C and the AA genotype of –1438 G/A polymorphism might be a factor in clinical severity of OCD.
A polymorphism of serotonin transporter was studied in 226 patients with affective disorders (n = 132 for bipolar, n = 94 for unipolar affective disorder) and in 213 healthy subjects. Consensus diagnosis by at least two psychiatrists, according to the ICD-10 and DSM-IV criteria was made for each patient using SCID (Structured Clinical Interview for DSM-IV Axis I Disorders). A functional polymorphism in the promoter region of serotonin transporter gene, where 44 bp are either inserted (long allele) or deleted (short allele) was analysed. Genotype s/s was significantly more frequent in patients comparing to the control group (P = 0.011 for bipolar and P = 0.003 for unipolar affective disorder) - the most marked association was found in males with bipolar and unipolar illness. The allele frequencies also differ significantly between patients and controls (P = 0.003 for bipolar and P = 0.001 for unipolar affective disorder). The frequency of the low activity (short) allele was higher in patients than in controls (51.1% in bipolar, and 54.3 in unipolar vs 39.4% in controls). We suggest that the presence of allele s may increase the susceptibility to occurrence of affective disorder.
Suicidal behavior is a major health problem worldwide. The risk of suicide-related behavior is supposed to be determined by a complex interplay of sociocultural factors, psychiatric history, personality traits, and genetic vulnerability. Family and twin studies point towards a partial heritability of suicidal behavior. First molecular genetic studies concentrated on genes of the serotonergic system based on the biochemical evidence that serotonergic neurotransmission is implicated in this behavior. Furthermore, genes of e.g. the dopaminergic and noradrenergic neurotransmitter systems have also been the subject of investigations in this context. The aim of this article is to review molecular genetic studies in suicidal behavior beyond the serotonergic system and to emphasize findings on new genes.
In a modified case–control association study we tested the assumption that two polymorphisms (A118G in exon 1 and IVS2+31 in intron 2) of the human μ-opioid receptor gene (OPRM1) confer susceptibility to opioid dependence.
In contrast to classical case–control studies both groups, opioid dependent cases and non-opioid dependent controls were recruited from individuals who have had access to drugs including opioids and who had been sentenced for violation of the “Dangerous Drugs Act” in Germany.
For the two allelic variants of OPRM1 under study we did not find evidence for association with opioid dependence.
Despite absence of association we think that this recruitment approach introduced here, is useful since it putatively offers a more adequate matching for case–control association studies of opioid dependent individuals.
Brain-derived neurotrophic factor (BDNF) gene variants may potentially influence behaviour. In order to test this hypothesis, we investigated the relationship between BDNF Val66Met polymorphism and aggressive behaviour in a population of schizophrenic patients. Our results showed that increased number of BDNF Met alleles was associated with increased aggressive behaviour.
Dystrobrevin binding protein 1 (DTNBP1), or dysbindin, is thought to be critical in regulating the glutamatergic system. While the dopamine pathway is known to be important in the aetiology of schizophrenia, it seems likely that glutamatergic dysfunction can lead to the development of schizophrenia. DTNBP1 is widely expressed in brain, levels are reduced in brains of schizophrenia patients and a DTNBP1 polymorphism has been associated with reduced brain expression. Despite numerous genetic studies no DTNBP1 polymorphism has been strongly implicated in schizophrenia aetiology. Using a haplotype block-based gene-tagging approach we genotyped 13 SNPs in DTNBP1 to investigate possible associations with DTNBP1 and schizophrenia. Four polymorphisms were found to be significantly associated with schizophrenia. The strongest association was found with an A/C SNP in intron 7 (rs9370822). Homozygotes for the C allele of rs9370822 were more than two and a half times as likely to have schizophrenia compared to controls. The other polymorphisms showed much weaker association and are less likely to be biologically significant. These results suggest that DTNBP1 is a good candidate for schizophrenia risk and rs9370822 is either functionally important or in disequilibrium with a functional SNP, although our observations should be viewed with caution until they are independently replicated.
Fyn tyrosine kinase is a member of the Scr family that phosphorylates the NR2A and NR2B subunits of the NMDA receptors reducing the inhibitory effects of ethanol and therefore may regulate the individual sensitivity to ethanol.
To investigate whether there is any relationship between the polymorphism at position −93 of the Fyn kinase gene and the susceptibility to develop alcoholism.
We studied the distribution of genotypes and alleles of the polymorphism −93A/G (137346 T/C) in the 5′ UTR region of the fyn gene in 207 male heavy drinkers (119 with alcohol dependence and 88 with alcohol abuse) and 100 control subjects from Castilla y León (Spain).
The frequency of G allele carriers was higher in alcohol dependents than in alcohol abusers (47.9% vs 30.6%; p = 0.015; OR = 2.077; 95% CI 1.165–3.704).
Our results show that the −93G allele of Fyn kinase gene is associated with higher risk to develop alcohol dependence in Spanish men.