A genome-wide association study on lipoprotein (a) levels and coronary artery disease severity in a Chinese population[S]
A genome-wide association study on lipoprotein (a) levels and coronary artery disease severity in a Chinese population[S]
复制标题
中国人群脂蛋白 (a) 水平与冠状动脉疾病严重程度的全基因组关联研究
DOI：
10.1194/jlr.p091009
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发表时间：
2019-08-01
影响因子：
6.5
通讯作者：
Zhong, Shilong
中科院分区：
文献类型：
--
作者：
Liu, Yibin;Ma, Hongkun;Zhong, Shilong
脂蛋白（a）[Lp（a）]是冠心病（CAD）的遗传决定性危险因素。以前的全基因组关联研究（GWAS），主要是在高加索人中进行的，已经确定了许多Lp（a）相关的SNP。在此，我们对1,403名中国汉族受试者的Lp（a）水平进行了GWAS，并进一步探讨了Lp（a）相关SNP与CAD严重程度之间的关系。我们观察到，Lp（a）水平升高与TAXUS和心脏手术（SYNTAX）评分的经皮冠状动脉介入治疗以及严重钙化病变和长距离病变计数之间的协同作用显著相关（LRL; P < 0.05），其被定义为病变跨度>20 mm。此外，我们确定了四个独立的SNP，即rs7770628，rs73596816，LPA的rs6926458和SLC 22 A2的rs 144217738与Lp（a）水平显著相关。我们还发现rs7770628与高SYNTAX评分相关[比值比（OR）（95%CI）：1.37（1.05-1.80），P = 0.0213，错误发现率（FDR）= 0.0852]，rs7770628和rs73596816与携带LRL的高风险相关[OR（95%CI）：1.53（1.17-2.01），P = 0.0018，FDR = 0.0072和1.72（1.19-2.49），P = 0.0040，FDR = 0.0080]。我们的研究是一个大规模的GWAS，以确定中国汉族人群中的Lp（a）相关变异。我们的研究结果强调了脂蛋白（a）干预的重要性和潜力，并扩大了我们对CAD预防和治疗的理解。
Lipoprotein (a) [Lp(a)] is a genetically determined risk factor of coronary artery disease (CAD). Previous genome-wide association studies (GWASs), which were mostly carried out in Caucasians, have identified many Lp(a)-associated SNPs. Here, we performed a GWAS on Lp(a) levels and further explored the relationships between Lp(a)-associated SNPs and CAD severity in 1,403 Han Chinese subjects. We observed that elevated Lp(a) levels were significantly associated with the increased synergy between percutaneous coronary intervention with TAXUS and cardiac surgery (SYNTAX) score and the counts of heavily calcified lesions and long-range lesions (LRLs; P < 0.05), which are defined as lesions spanning >20 mm. Moreover, we identified four independent SNPs, namely, rs7770628, rs73596816, and rs6926458 in LPA, and rs144217738 in SLC22A2, that were significantly associated with Lp(a) levels. We also found that rs7770628 was associated with high SYNTAX scores [odds ratio (OR) (95% CI): 1.37 (1.05–1.80), P = 0.0213, false discovery rate (FDR) = 0.0852], and that rs7770628 and rs73596816 were associated with high risk of harboring LRLs [OR (95% CI): 1.53 (1.17–2.01), P = 0.0018, FDR = 0.0072 and 1.72 (1.19–2.49), P = 0.0040, FDR = 0.0080, respectively]. Our study was a large-scale GWAS to identify Lp(a)-associated variants in the Han Chinese population. Our findings highlight the importance and potential of Lp(a) intervention and expand our understanding of CAD prevention and treatment.