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

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

Research output: Contribution to journalArticle

22 Citations (Scopus)

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. Conclusion - 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.

Original languageEnglish (US)
Pages (from-to)948-954
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume26
Issue number4
DOIs
StatePublished - Apr 1 2006
Externally publishedYes

Fingerprint

Plasminogen Activator Inhibitor 1
Single Nucleotide Polymorphism
Coronary Disease
Haplotypes
Alleles
Genes
Smoking
Genetic Promoter Regions
Exons
Odds Ratio
Population

Keywords

  • Case-control
  • Coronary heart disease
  • Haplotype-based association study
  • Plasminogen activator inhibitor-1 gene
  • Tagging SNP

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Plasminogen activator inhibitor-1 gene selection of tagging single nucleotide polymorphisms and association with coronary heart disease. / Su, Shaoyong; Chen, Shufeng; Zhao, Jiangong; Huang, Jianfeng; Wang, Xiaoling; Chen, Runsheng; Gu, Dongfeng.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 26, No. 4, 01.04.2006, p. 948-954.

Research output: Contribution to journalArticle

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AB - 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. Conclusion - 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.

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