| Objective—Genetic architecture of coronary artery disease is still to be defined. Since LRP6 play critical roles in Wnt signal transduction which are important for vascular development and endodermis specification, we therefore resequenced it to search for accumulation of mutations in coronary artery disease patients compared with normal subjects.Methods—We systemically sequenced all the exons and promoter region of LRP6 gene in a sample of 380 coronary artery disease patients and 380 control subjects from Chinese.Result—In total, we identified 8 genetic variants, including 5 rare missense mutations such as K82N (one patient), S488Y(one patient), P1066T (two patient), P1206H (two patient),11264V (one patient). In silico analysis predicted that three patient-specific rare missense mutations (P1066T, P1206H and 11264V) and two common missense mutation (S817C and V10621) had damaging effect, while the other missense mutations were benign. In vitro functional analysis of the mutations detected was also performed. All the five patient specific missense mutation decreased Wnt signal activity.Conclusion—Our study suggests that defects in Wnt signal activation may be an important contributing factor for the onset of coronary artery disease. Further investigations in larger cohorts will be needed in order to define the specific phenotypic characteristics potentially correlated with reduced Wnt signalling. Objective—The aim of the present study was to explore whether genetic polymorphisms of lymphotoxin alpha (LTA) gene are a risk factor for ischemic stroke in Han Chinese population.Methods—Three common variants of LTA, rs1800683,rs909253 and rs 1041981,were genotyped in a sample including 558 ischemic stroke cases and 557 normal controls using Taqman-MGB assay in a case-control study. The association analyses were performed at both single nucleotide polymorphism and haplotype levels. Bonferroni correction was applied for multiple corrections.Result—No signicant association were found between any of these LTA alleles or genotypes with risk of ischemic stroke. When AGA haplotype was chosen as the baseline for adjusting conventional risk factors, the protective effect for haplotype GGC remained significant (AGA versus GGC; OR,0.381; 95% CI,0.198 to 0.733; p=0.003),Conclusion—The GGC haplotype of LTA maybe a protective factor in pathogenesis of ischemic stroke warrants further confirm in a prospective study. Objective—Common polymorphisms within cytochrome P450 2J2 (CYP2J2) and epoxide hydrolase 2 (EPHX2), which are involved in the generation or hydrolysis of EET, may determine susceptibility to development of cardiovascular disease. To derive a more precise estimation of their relationship, we undertook a case-control study as well as a meta-analysis to assess possible associations of CAD risk with CYP2J2 and EPHX2 genetic variations.Methods—Associations between 4 single nucleotide polymorphisms (SNPs) in CYP2J2 and 5 in EPHX2 with CAD were examined in a total of 1344 case subjects and 1267 ethnically and geographically matched controls. To further confirm the effect of two functional variants (G-50T and R287Q) in the development of CAD, we conducted a meta-analysis including 7 studies on G-50T polymorphism and 6 studies on R287Q polymorphism before June 2010.Result—No significant association between common polymorphisms within these two genes and CAD was observed in our sample, either using methods of single locus analysis or haplotype-based analysis. In addition, no association was detected in our meta analysis between these two functional variants and risk of developing CAD.Conclusion—The present case control study as well as meta analysis suggested no association between CYP 2J2 G-50T and EPHX2 R287Q and CAD risk.
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