X Chen1, S Li, Y Yang, X Yang, Y Liu, Y Liu, W Hu, L Jin, X Wang. 1. MOE Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Abstract
BACKGROUND: Genetic variants influencing lipid levels and risk of coronary artery disease (CAD) have been identified by recent genome-wide association studies (GWAS). OBJECTIVES: To test the association of single nucleotide polymorphisms (SNPs) implicated in lipoprotein metabolism and CAD in GWAS with atherosclerotic cardiovascular disease (ASCVD, including ischemic stroke [IS] and myocardial infarction [MI] phenotypes). PATIENTS AND METHODS: A two-stage genetic association study was conducted in the Chinese Hans population. Stage I included a cohort with 451 IS cases and 462 controls for association analysis using 92 SNPs. Stage II examined the associations of eight positive variants and five additional variants with IS, MI and ASCVD in a cohort with 779 IS cases and 836 controls and a cohort with 824 MI cases and 737 controls. RESULTS: The T allele of rs4731702 located near the KLF14 gene was associated with a decreased risk of MI with an odds ratio (OR) of 0.72 (P<3.85×10(-3)). The rs4731702-T allele was also associated with a decreased risk of ASCVD with an OR of 0.78 (Pmeta-analysis<5.43×10(-4)). In addition, we found that a missense variant of KLF14, rs111400400 (Ser58Pro), was associated with MI. CONCLUSION: Genetic variants newly identified near/in the KLF14 gene were implicated in the aetiology of atherosclerotic-related phenotypes.
BACKGROUND: Genetic variants influencing lipid levels and risk of coronary artery disease (CAD) have been identified by recent genome-wide association studies (GWAS). OBJECTIVES: To test the association of single nucleotide polymorphisms (SNPs) implicated in lipoprotein metabolism and CAD in GWAS with atherosclerotic cardiovascular disease (ASCVD, including ischemic stroke [IS] and myocardial infarction [MI] phenotypes). PATIENTS AND METHODS: A two-stage genetic association study was conducted in the Chinese Hans population. Stage I included a cohort with 451 IS cases and 462 controls for association analysis using 92 SNPs. Stage II examined the associations of eight positive variants and five additional variants with IS, MI and ASCVD in a cohort with 779 IS cases and 836 controls and a cohort with 824 MI cases and 737 controls. RESULTS: The T allele of rs4731702 located near the KLF14 gene was associated with a decreased risk of MI with an odds ratio (OR) of 0.72 (P<3.85×10(-3)). The rs4731702-T allele was also associated with a decreased risk of ASCVD with an OR of 0.78 (Pmeta-analysis<5.43×10(-4)). In addition, we found that a missense variant of KLF14, rs111400400 (Ser58Pro), was associated with MI. CONCLUSION: Genetic variants newly identified near/in the KLF14 gene were implicated in the aetiology of atherosclerotic-related phenotypes.
Authors: Julian C van Capelleveen; Andrea E Bochem; M Mahdi Motazacker; G Kees Hovingh; John J P Kastelein Journal: Curr Atheroscler Rep Date: 2013-06 Impact factor: 5.113