Abstract
There is increasing evidence suggesting the importance of evaluating gene–environment
interactions in the genetic study of coronary artery disease (CAD). We investigated
the association of multiple single nucleotide polymorphisms in the angiotensinogen
(AGT) gene with CAD, considering the interaction between the genetic and non-genetic
factors, using a larger and ethnically homogeneous angiographic cohort. A total of
1254 consecutive patients who underwent cardiac catheterization (735 with CAD and
519 without) were recruited. T174M (rs4762), M235T (rs699), G-6A, A-20C, G-152A, and
G-217A polymorphisms of the AGT gene were genotyped. We used a regression approach
based on a generalized linear model to evaluate haplotype effects defined by the multilocus
data and detection of gene–environment interaction by incorporating interaction terms
in the model. We found significant differences in global AGT gene haplotype profile
between patients with and without CAD (the global score statistic = 25.411, P = 0.008). Significant interactions between AGT gene haplotypes, gender and hypertension
were detected. We also used haplotype counting to directly estimate the odds ratio
of each AGT gene haplotype, and found that the effects of haplotypes were markedly
different in subgroups defined by gender and hypertension, providing strong evidence
of gene–environment interaction. Female gender synergistically enhances (or male gender
reverses) the effects of AGT gene haplotypes on the risk of CAD in the presence of
hypertension. In conclusion, the effect of AGT gene haplotypes on the risk of CAD
was significantly increased in women with hypertension, which highlights the importance
of evaluating gene–environment interactions in the genetic study of CAD.
Keywords
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Article info
Publication history
Published online: July 24, 2008
Accepted:
June 4,
2008
Received in revised form:
June 3,
2008
Received:
January 3,
2008
Identification
Copyright
© 2008 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
