A genetic variant in the gene encoding fibrinogen beta chain predicted development of hypertension in Chinese men

Kwok Leung Ong; Annette W. K. Tso; Stacey S. Cherny; Pak Chung Sham; Karen S. L. Lam; Chao Qiang Jiang; Neil G. Thomas; Tai Hing Lam; Bernard M. Y Cheung

doi:10.1160/TH09-10-0692

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 103(04): 728-735
DOI: 10.1160/TH09-10-0692

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

A genetic variant in the gene encoding fibrinogen beta chain predicted development of hypertension in Chinese men

Kwok Leung Ong

¹Department of Medicine, University of Hong Kong, Hong Kong

,

Annette W. K. Tso

¹Department of Medicine, University of Hong Kong, Hong Kong

,

Stacey S. Cherny

²Department of Psychiatry and Genome Research Centre, University of Hong Kong, Hong Kong

,

Pak Chung Sham

²Department of Psychiatry and Genome Research Centre, University of Hong Kong, Hong Kong

,

Karen S. L. Lam

¹Department of Medicine, University of Hong Kong, Hong Kong

,

Chao Qiang Jiang

³Guangzhou no. 12 Hospital, Guangzhou, China

,

Neil G. Thomas

⁴Department of Public Health and Epidemiology, University of Birmingham, UK

,

Tai Hing Lam

⁵Department of Community Medicine, University of Hong Kong, Hong Kong

,

Bernard M. Y Cheung

¹Department of Medicine, University of Hong Kong, Hong Kong

› Author Affiliations

Abstract

Summary

Fibrinogen, a major determinant of blood viscosity, is an acute phase protein associated with cardiovascular disease. We studied the association of hypertension with single nucleotide polymorphisms (SNPs) in the gene encoding the fibrinogen β chain (FGB). Three tagging SNPs (rs1025154, rs4220 and rs1044291) were selected from the HapMap database on Han Chinese. Genotypes were determined in 1,294 unrelated subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort. There were 199 hypertensive subjects at baseline. Among 1,095 subjects normotensive at baseline, 178 developed hyper-tension during a median follow-up period of 6.4 years. Among the three tagging SNPs, rs4220 showed significant association with hypertension at both baseline (odds ratio [OR]=1.49, p=0.004) and at follow-up (OR=1.32, p=0.013). The minor A allele of this SNP was associated with higher plasma fibrinogen level (β=0.144, p<0.001 at baseline and β=0.130, p<0.001 at follow-up). Among subjects normotensive at baseline, this SNP was also associated with the development of hyper-tension in men (OR=1.52, p=0.022), but not in women. The SNP rs4220 in FGB, which leads to the substitution of arginine by lysine at position 448, is independently associated with plasma fibrinogen level and hypertension in Hong Kong Chinese. This suggests a possible causal role of fibrinogen in hypertension development, especially in men.

Keywords

Fibrinogen - hypertension - single nucleotide polymorphisms

Full Text

References

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