Angiotensin II type I receptor gene and myocardial infarction: Tagging SNPs and haplotype based association study. The Beijing atherosclerosis study

Shaoyong Su, Jianhong Chen, Jiangong Zhao, Jianfeng Huang, Xiaoling Wang, Runsheng Chen, Dongfeng Gu

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)673-681
Number of pages9
JournalPharmacogenetics
Volume14
Issue number10
DOIs
StatePublished - Oct 1 2004

Fingerprint

Angiotensin I
Angiotensin Receptors
Haplotypes
Single Nucleotide Polymorphism
Atherosclerosis
Myocardial Infarction
Genes
Linkage Disequilibrium
Beijing
Odds Ratio

Keywords

  • Angiotensin II type I receptor gene
  • Case-control
  • Haplotype tagging SNP
  • Haplotype-based association test
  • Myocardial infarction

ASJC Scopus subject areas

  • Genetics
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Angiotensin II type I receptor gene and myocardial infarction : Tagging SNPs and haplotype based association study. The Beijing atherosclerosis study. / Su, Shaoyong; Chen, Jianhong; Zhao, Jiangong; Huang, Jianfeng; Wang, Xiaoling; Chen, Runsheng; Gu, Dongfeng.

In: Pharmacogenetics, Vol. 14, No. 10, 01.10.2004, p. 673-681.

Research output: Contribution to journalArticle

Su, Shaoyong ; Chen, Jianhong ; Zhao, Jiangong ; Huang, Jianfeng ; Wang, Xiaoling ; Chen, Runsheng ; Gu, Dongfeng. / Angiotensin II type I receptor gene and myocardial infarction : Tagging SNPs and haplotype based association study. The Beijing atherosclerosis study. In: Pharmacogenetics. 2004 ; Vol. 14, No. 10. pp. 673-681.
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AB - 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.

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