Diplotype Trend Regression Analysis of the ADH Gene Cluster and the ALDH2 Gene: Multiple Significant Associations with Alcohol Dependence

Abstract Background: Alcohol dependence (AD) poses a serious medical problem and significant public health issue contributing to morbidity and mortality throughout the world. The aim of the study is to test the association of rs698 (ADH1C) and rs671(ALDH2) with the risk of alcohol dependence and to further assess the influence of environmental factors on altering the genetic susceptibility to alcoholism in south Indian Tamilian population.Methods& Results: A total of 150 alcohol dependent cases aged between 18- and 65-years fulfilling DSM-V criteria were recruited from de addiction center. Subjects in control group (n=150) had history of alcohol intake with AUDIT score less than 8. The alleles were genotyped using TaqMan SNP genotyping assays by quantitative PCR. Association with alcohol dependence was evaluated with various genetic models using chi-square test. Multiple logistic regression analysis was performed to explore the effect of covariates. The dominant (OR=0.5811,95% CI: 0.372-0.9224, p<0.01) and allelic genetic model (OR=0.6228,95% CI: 0.4328-0.9009, p<0.01) of ALDH2, rs671 between cases and controls showed a significant association of the genetic variant with AD. Multivariate logistic regression analysis revealed education level, family history, marital status were significantly associated with AD but there was no association between rs671 genotypes in the presence of these co-variates.Conclusions: Genetic factors play an important role in alcohol dependence. Combined analysis of functional genetic variants and environmental factors is warranted in future studies.

Download Full-text

Associations Between ADH Gene Variants and Alcohol Phenotypes in Dutch Adults

Twin Research and Human Genetics ◽

10.1375/twin.13.1.30 ◽

2010 ◽

Vol 13 (1) ◽

pp. 30-42 ◽

Cited By ~ 14

Author(s):

Jenny H. D. A. van Beek ◽

Gonneke Willemsen ◽

Marleen H. M. de Moor ◽

Jouke Jan Hottenga ◽

Dorret I. Boomsma

Keyword(s):

Alcohol Consumption ◽

Gene Cluster ◽

Problem Drinking ◽

Age At Onset ◽

Sample Survey ◽

Gene Sets ◽

Adh Gene ◽

Australian Sample ◽

Dutch Sample ◽

A Minor

AbstractRecently, Macgregor et al. (2009) demonstrated significant associations of ADH polymorphisms with reactions to alcohol and alcohol consumption measures in an Australian sample. The aim of the present study was to replicate these findings in a Dutch sample. Survey data on alcohol phenotypes came from 1,754 unrelated individuals registered with the Netherlands Twin Register. SNPs in the ADH gene cluster located on chromosome 4q (n= 491) were subdivided in seven gene sets: ADH5, ADH4, ADH6, ADH1A, ADH1B, ADH1C and ADH7. Within these sets associations of SNPs with alcohol consumption measures, age at onset variables, reactions to alcohol and problem drinking liability were examined. Of the original 38 SNPs studied by Macgregor et al. (2009), six SNPs were not available in our dataset, because one of them had a minor allele frequency < .01 (rs1229984) and five could not be imputed. The remaining SNP associations with alcohol phenotypes as identified by Macgregor et al. (2009) were not replicated in the Dutch sample, after correcting for multiple genotype and phenotype testing. Significant associations were found however, for reactions to alcohol with a SNP in ADH5 (rs6827292,p= .001) and a SNP just upstream of ADH5 (rs6819724,p= .0007) that is in strong LD with rs6827292. Furthermore, an association between age at onset of regular alcohol use and a SNP just upstream of ADH7 (rs2654849,p= .003) was observed. No significant associations were found for alcohol consumption and problem drinking liability. Although these findings do not replicate the earlier findings at the SNP level, the results confirm the role of the ADH gene cluster in alcohol phenotypes.

Download Full-text

Association of the gamma-aminobutyric acid A receptor gene cluster with alcohol dependence in Taiwanese Han

Molecular Psychiatry ◽

10.1038/sj.mp.4001110 ◽

2002 ◽

Vol 7 (8) ◽

pp. 828-829 ◽

Cited By ~ 9

Author(s):

Y T Chang ◽

H S Sun ◽

C S J Fann ◽

C-J Chang ◽

Z H Liao ◽

...

Keyword(s):

Alcohol Dependence ◽

Gene Cluster ◽

Receptor Gene ◽

Aminobutyric Acid ◽

Gamma Aminobutyric Acid

Download Full-text

Functional polymorphisms of the APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster are associated with dyslipidemia in a sex-specific pattern

PeerJ ◽

10.7717/peerj.6175 ◽

2019 ◽

Vol 6 ◽

pp. e6175

Author(s):

Wei Bai ◽

Changgui Kou ◽

Lili Zhang ◽

Yueyue You ◽

Weiying Yu ◽

...

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Gene Cluster ◽

Logistic Regression Analysis ◽

Gene Polymorphisms ◽

Serum Lipid ◽

Male And Female ◽

Low Hdl ◽

The Relationship ◽

Cluster Gene

Background Dyslipidemia contributes to the risk of many diseases, including stroke, cardiovascular disease and metabolic-related diseases. Previous studies have indicated that single nucleotide polymorphisms (SNPs) are associated with different levels of serum lipid. Therefore, this study explored the relationship between the APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster gene polymorphisms and dyslipidemia in the total sample population and stratified by genders in a northeast Chinese population. Methods A total of 3,850 participants from Jilin Province, China, were enrolled in our study, and their serum lipid levels were measured. Six functional SNPs (APOA1 rs5072, APOC3 rs5128, APOA4 rs5104, APOA5 rs651821, ZPR1 rs2075294 and BUD13 rs10488698) were genotyped using polymerase chain reaction and MALDI-TOF-MS. Logistic regression analysis was performed to explore the relationship of APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster gene polymorphisms with dyslipidemia. Linkage disequilibrium and haplotype analyses were performed with the SNPStats program and Haploview software. Results All SNPs conformed to Hardy–Weinberg equilibrium. Logistic regression analysis revealed that rs5072, rs5128 and rs651821 were associated with hypertriglyceridemia, rs5104 and rs651821 were associated with low-HDL cholesterolemia in overall group. rs651821 was associated with hypertriglyceridemia and low-HDL cholesterolemia in both the male and female group. However, among females, rs5072 was observed to be associated with hypertriglyceridemia. Haplotype analysis showed that haplotypes TGCCGC and CAGCGC were associated with dyslipidemia in the overall, male and female groups. Conclusion SNPs in the APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster were associated with dyslipidemia. Furthermore, the association of APOA1 rs5072 in this gene cluster with dyslipidemia differed between genders; thus, additional studies are needed to confirm this conclusion, and the mechanisms underlying these results warrant further exploration.

Download Full-text