胱硫醚合成酶启动子上的功能多态性位点显著降低中国汉族人群的先天性心脏病易感性.docVIP

 A Functional Variant in the Cystathionine b-Synthase Gene Promoter Significantly Reduces Congenital Heart Disease 5 10 15 20 25 30 35 40 Susceptibility in a Han Chinese Population# ZHAO Jianyuan1, YANG Xueyan1, SHI Kaihu2, SUN Shuna3, HOU Jia3, WANG Jue1, YE Zhizhou1, DUAN Wenyuan4, CHEN Yijiang5, SHEN Hongbing6, QIAO Bin4, HUANG Guoying3, JIN Li1, WANG Hongyan1** (1. The State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, ShangHai 200433; 2. The Second Hospital of Anhui Medical University, HeFei 230601; 3. Children’s Hospital of Fudan University, ShangHai 200032; 4. Institute of Cardiovascular Disease General Hospital of Jinan Military, JiNan 250000; 5. Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, NanJing 210029; 6. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, NanJing 210029) Abstract: Homocysteine is an independent risk factor for various cardiovascular diseases. There are two ways to remove homocysteine from embryonic cardiac cells: remethylation to form methionine or transsulfuration to form cysteine. Cystathionine β-synthase (CBS) catalyzes the first step of homocysteine transsulfuration as a rate-limiting enzyme. In this study, we identified a functional variant -4673CG (rs2850144) in the CBS gene promoter region that significantly reduces the susceptibility to congenital heart disease (CHD) in a Han Chinese population consisting of 2,340 CHD patients and 2,270 controls. Individuals carrying the heterozygous CG and homozygous GG genotype had a 15% (OR=0.85, 95%CI=0.75-0.96, P=0.011) and 40% (OR=0.60, 95% CI=0.49-0.73, P=1.78×10-7) reduced risk to develop CHD than the wild-type CC genotype carriers in the combined samples, respectively. Additional stratified analyses demonstrated that CBS -4673CG is significantly related to septation defects and co