Objectives The present study aimed to assess the effect
of haplotype variation in angiotensin II type I receptor
(AGTR1) gene on the risk of myocardial infarction (MI) in
Chinese males.
Methods We used 48 patients to identify the putative
functional polymorphisms in AGTR1 gene by direct
sequencing. The program tagSNPs was used to identify an
optimal set of tagging single nucleotide polymorphisms
(SNPs). These selected SNPs were then genotyped in 419
male patients with MI and 400 age-matched male controls.
The program haplo.stats was used to investigate the
relationship between the haplotypes and MI.
Results Sixteen polymorphisms in AGTR1 gene were
identified. Based on the linkage disequilibrium pattern
among these SNPs, six polymorphisms, SNP1, SNP6–
SNP7 and SNP13–SNP15, were selected as haplotype
tagging SNPs and further genotyped. Single SNP analyses
indicated that the SNP1, SNP6 and SNP13 were
significantly associated with MI, adjusted for covariates.
Haplotype-based association analyses identified the
frequency of haplotype AGATAA was lower in cases than in
controls (P 0.006). In comparison, three haplotypes
(AAATAA, TAGCAA and AAACAG) were found to
significantly increase the risk of MI with adjusted odds
ratio equal to 1.33, 1.75 and 2.64, respectively (P 0.029,
0.026 and 0.015).
Conclusions Our study suggests that common genetic
variations in the AGTR1 gene may affect the risk of MI in
Chinese males, and that there might be several functional
variants in AGTR1 gene and the combined effect of these
variants seemed to have a larger effect on the risk of MI in
Chinese males. Pharmacogenetics 14:673–681 & 2004
Lippincott Williams & Wilkins