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PLoS One. 2014 Jul 21;9(7):e103161. doi: 10.1371/journal.pone.0103161. eCollection 2014.

Synergistic association between two alcohol metabolism relevant genes and coronary artery disease among Chinese hypertensive patients.

Author information

1
Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
2
Department of Etiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
3
Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
4
The Third Division of Cardiology, Department of Internal Medicine, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, China.
5
State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

OBJECTIVE:

Coronary artery disease (CAD) is a multifactorial and polygenic disease. The aim of this study was to examine the association between six polymorphisms of four alcohol metabolism relevant genes (ADH1B, ADH1C, ALDH1b1, ALDH2) and the risk of CAD in Han Chinese.

METHODS AND RESULTS:

This was a hospital-based case-control study involving 1365 hypertensive patients. All study subjects were angiographically confirmed. Genotypes were determined with ligase detection reaction method. There was no observable deviation from the Hardy-Weinberg equilibrium for six examined polymorphisms in controls. The genotype and allele distributions of ALDH1b1 rs2073478 and ALDH2 rs671 polymorphisms differed significantly between the two groups (P≤0.005), even after the Bonferroni correction. The most common allele combination was A-C-C-G-C-G (alleles in order of rs1229984, rs1693482, rs2228093, rs2073478, rs886205, rs671) and its frequency was slightly higher in controls than in CAD patients (P = 0.067). After assigning the most common allele combination as a reference, allele combination A-C-C-T-C-A, which simultaneously possessed the risk alleles of rs2073478 and rs671 polymorphisms, was associated with a 1.80-fold greater risk of CAD. Further, a two-locus model including rs2073478 and rs671 that had a maximal testing accuracy of 0.598 and a cross-validation consistency of 10 (P = 0.008) was deemed as the overall best MDR model, which was further validated by classical Logistic regression model.

CONCLUSION:

Our findings provide clear evidence for both individual and interactive associations of ALDH1b1 and ALDH2 genes with the development of CAD in Han Chinese.

PMID:
25047496
PMCID:
PMC4105442
DOI:
10.1371/journal.pone.0103161
[Indexed for MEDLINE]
Free PMC Article
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