This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 26/4/948    most recent 01.ATV.0000204731.17646.f2v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Su, S. Articles by Gu, D. Search for Related Content PubMed PubMed Citation Articles by Su, S. Articles by Gu, D. Related Collections Risk Factors Epidemiology Coagulation and fibronolysis Genetics of cardiovascular disease

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:948.)
© 2006 American Heart Association, Inc.

Thrombosis

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

From the Division of Population Genetics and Prevention (S.S., S.C., J.Z., J.H., X.W., D.G.), Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; National Human Genome Center at Beijing (S.S., D.G.), China; and Institute of Biophysics (R.C.), Chinese Academy of Sciences, Beijing, China.

Correspondence to Dongfeng Gu, MD, MS, Professor and Chair, Division of Population genetics and Prevention, Cardiovascular Institute and Fu Wai Hospital, No. 167 Beilishi Rd, Beijing, 100037, PR China. E-mail gudf{at}yahoo.com

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.

We examined the association of 5 tagging SNPs of PAI-1 gene with coronary heart disease (CHD) in 816 patients and 937 controls. A significant interaction between PAI-1 gene and smoking status was identified, with rs2227631 A allele and rs1799889 4G allele increasing the risk of CHD among nonsmokers in Chinese.

Key Words: coronary heart disease • plasminogen activator inhibitor-1 gene • tagging SNP • haplotype-based association study • case-control

This article has been cited by other articles:

				P.E. Morange, N. Saut, M.C. Alessi, J.S. Yudkin, M. Margaglione, G. Di Minno, A. Hamsten, S.E. Humphries, D.A. Tregouet, and I. Juhan-Vague Association of Plasminogen Activator Inhibitor (PAI)-1 (SERPINE1) SNPs With Myocardial Infarction, Plasma PAI-1, and Metabolic Parameters: The HIFMECH Study Arterioscler. Thromb. Vasc. Biol., October 1, 2007; 27(10): 2250 - 2257. [Abstract] [Full Text] [PDF]