Background Genetic factors contribute to the development of coronary artery disease （CAD）.Recently,a missense mutation in the low density lipoprotein receptor related protein 6 （LRP6） gene,encoding low density lipoprotein receptor related protein 6,has been implicated in an autosomal dominant form of early-onset CAD.The aim of this study was to determine whether the common variants in LRP6 are associated with sporadic CAD in Chinese.Methods A total of 766 CAD patients and 806 healthy controls were included in this study.The presence of angiographic CAD was determined by coronary angiographic analysis.Six signal nucleotide polymorphisms （SNPs） were genotyped using the polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） technique.Results A significant association was detected between rs11054731 in LRP6 intron 2 and CAD in our cohort （P=0.001）.The CC genotype and C allele frequency in the case group were 52% and 72%.Using a dominant model of inheritance,the C allele of rs11054731 was shown to be an independent risk factor for CAD with an OR of 1.45 （95% CI：1.19-1.77,P=0.0002）.With the stratification according to the number of affected coronary arteries,an association was observed between rs11054731 and CAD （P=0.0002）.No significant association was observed between any other SNPs and the risk of CAD.Conclusion The C allele of the rs11054731 within the LRP6 gene was associated with increased risk and extent of CAD in Chinese.
Wang HuiLiu Qi-jiChen Min-zhiLi LiZhang KaiCheng Guang-huiMa LongGong Yao-qin
目的在27例儿茶酚胺介导的多形性室速患者及家庭成员中寻找CASQ2基因突变。方法应用直接DNA序列分析对临床诊断为家族性多形性室速27例患者及家庭成员进行进行基因突变分析。应用Taqman基因分型检测在以1400名正常人群中确定CASQ2变异的频率。结果在一个多形性室速家系中发现了1个新的杂合子改变F189L。通过与多种生物比对，证实该改变发生于在第2结构域一个高度保守的氨基酸上，位于第5外显子的F189L的改变，使编码蛋白的第189位氨基酸由苯丙氨酸改变为亮氨酸。应用Taqman SNP genotyping assay分析方法证实正常人群1400名中未发现同样改变。在CASQ2基因中未发现其他引起疾病的基因突变。结论发现了CASQ2基因的1个新F189L突变。
