Polygenetic regression model of renin-angiotensin system genes and the risk of XXXX in a large angiographic population.

@entity1 @entity7744 @entity1289 @entity7742 @entity29109 @entity2178 @entity26701 @entity26201 @entity26203 @entity453 @entity7743 @entity26200
BACKGROUND: Polygenetic effect has rarely been addressed in the genetic studies of @entity453 ( @entity453 ). We used the largest and ethnically homogeneous angiographic cohort to analyze multilocus data in renin-angiotensin system genes, and provide an explicit demonstration of gene-gene interactions. METHODS: A total of 1254 consecutive @entity1 who underwent cardiac catheterization (735 with @entity453 and 519 without) were recruited. Angiotensin converting enzyme( @entity1289 ) gene I/D polymorphism; @entity26203 , @entity7742 , @entity29109 , @entity26201 , @entity26701 , and @entity26200 polymorphisms of the @entity2178 ( @entity2178 ) gene; and @entity7744 polymorphism of the angiotensin II type I receptor ( @entity7743 ) gene were genotyped. We used a regression approach based on a generalized linear model to evaluate haplotype effects, adjust non-genetic confounding effects and detect gene-gene interaction between @entity1289 and @entity7743 genes. RESULTS: We found significant differences in global @entity2178 gene haplotype profile and individual haplotypes between cases and controls. Significant two-way and three-way gene-gene interactions between @entity1289 I/D, @entity7743 @entity7744 polymorphisms and @entity2178 gene haplotypes were detected. However, subjects carrying both D allele and GGCATC haplotype had an increased risk of @entity453 (odds ratio=1.63 [1.16-2.29]; P=0.004). We also used haplotype counting to directly estimate the odds ratio of each specific @entity2178 gene haplotype, and found that the effects of haplotypes were markedly different in subgroups with different @entity1289 or @entity7743 gene genotype. CONCLUSIONS: The regression-based haplotype analyses permits simultaneous dectection of multi-locus and multi-gene effects in determining the risk of @entity453 . We provide the paradigm for genetic studies of complex-trait diseases using candidate genes based on biological pathways.
