背景:冠状动脉钙化(CAC)是动脉粥样硬化的高度特异性标志物。Niemann-PickC1样1(NPC1L1)和3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR)是依泽替米贝和他汀类药物的治疗靶标,分别,这对动脉粥样硬化的进展很重要。然而,CAC对上述目标的遗传易感性仍然未知。我们的目的是研究NPC1L1和HMGCR基因多态性与早产三血管疾病(PTVD)患者CAC的相关性。
方法:在872例PTVD患者中,对NPC1L1的四种单核苷酸多态性(SNP)(rs11763759,rs4720470,rs2072183,rs2073547)和MGCR的三个SNP(rs12916,rs2303151,rs4629571)进行基因分型。根据冠状动脉造影结果,将患者分为低度CAC组和高度CAC组。
结果:共有872例PTVD患者(平均年龄,47.71±6.12;男性,72.8%)最终纳入分析。多因素logistic回归分析显示,NPC1L1和HMGCR基因的SNPs与总人群中高度CAC无显著相关性(P>0.05)。性别亚组分析表明,NPC1L1基因rs4720470的变异基因型(TT/CT)仅与男性患者的高度CAC风险增加有关(OR=1.505,95%CI:1.008-2.249,P=0.046)。但是在女性人群中没有发现显著的关联,NPC1L1和HMGCR基因的其他SNPs(均P>0.05)。
结论:我们首次报道NPC1L1基因rs4720470与男性PTVD患者的高度CAC相关。在未来,与该靶点相关的治疗是否可以减少CAC和心血管事件,值得进一步研究.
BACKGROUND: Coronary artery calcification (CAC) is a highly specific marker of atherosclerosis. Niemann-Pick C1-like 1 (
NPC1L1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) are the therapeutic targets of ezetimibe and statins, respectively, which are important for the progression of atherosclerosis. However, CAC\'s genetic susceptibility with above targets is still unknown. We aimed to investigate the association of
NPC1L1 and HMGCR gene polymorphisms with CAC in patients with premature triple-vessel disease (PTVD).
METHODS: Four single nucleotide polymorphisms (SNPs) (rs11763759, rs4720470, rs2072183, rs2073547) of NPC1L1, and three SNPs (rs12916, rs2303151, rs4629571) of HMGCR were genotyped in 872 PTVD patients. According to the coronary angiography results, patients were divided into low-degree CAC group and high-degree CAC group.
RESULTS: A total of 872 PTVD patients (mean age, 47.71 ± 6.12; male, 72.8%) were finally included for analysis. Multivariate logistic regression analysis showed no significant association between the SNPs of
NPC1L1 and HMGCR genes and high-degree CAC in the total population (P > 0.05). Subgroup analysis by gender revealed that the variant genotype (TT/CT) of rs4720470 on
NPC1L1 gene was associated with increased risk for high-degree CAC in male patients only (OR = 1.505, 95% CI: 1.008-2.249, P = 0.046) in dominant model, but no significant association was found in female population, other SNPs of NPC1L1 and HMGCR genes (all P > 0.05).
CONCLUSIONS: We reported for the first time that the rs4720470 on
NPC1L1 gene was associated with high-degree CAC in male patients with PTVD. In the future, whether therapies related to this target could reduce CAC and cardiovascular events deserves further investigation.