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Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):948-54. Epub 2006 Jan 19.

Plasminogen activator inhibitor-1 gene: selection of tagging single nucleotide polymorphisms and association with coronary heart disease.

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  • 1Division of Population genetics and Prevention, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Abstract

OBJECTIVE:

To explore the effect of plasminogen activator inhibitor-1 (PAI-1) gene variations on the risk of coronary heart disease (CHD) in Chinese Han population.

METHODS AND RESULTS:

We screened all exons and the promoter region of PAI-1 gene in 48 patients and identified 17 polymorphisms. Five tagging single nucleotide polymorphisms were selected and genotyped in 816 patients with CHD and 937 controls. In the total sample, no main effects of the loci or haplotypes reached statistical significance after adjusting environmental covariates. However, a strongly significant gene-smoking interaction was observed. Among nonsmokers, 2 polymorphisms located at promoter region (rs2227631 and rs1799889) showed significant association with CHD. The cases had higher frequency of rs2227631 A allele and rs1799889 4G allele than the controls (0.42 versus 0.33, P=0.001; 0.60 versus 0.52, P=0.002). Haplotype analyses confirmed the effects of the PAI-1 gene-smoking interaction on CHD risk. Compared with the most common haplotype G-5G-A-A-T (35.1%), the haplotype A-4G-A-A-C (32.7%) significantly increased the risk of CHD with adjusted odds ratio of 1.51 (95% CI, 1.12 to 2.05; P=0.008) in nonsmokers.

CONCLUSIONS:

This study identified a significant interaction between PAI-1 gene and smoking status. Both single locus and haplotype analyses indicated that rs2227631 A allele and rs1799889 4G allele increased the risk of CHD among nonsmokers in Chinese.

PMID:
16424345
[PubMed - indexed for MEDLINE]
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