Zhao Xueyan, Xu Jingjing, Tang Xiaofang, Huang Keyong, Li Jiawen, Liu Ru, Jiang Lin, Zhang Yin, Wang Dong, Sun Kai, Xu Bo, Zhao Wei, Hui Rutai, Gao Runlin, Song Lei, Yuan Jinqing
State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Cardiovasc Med. 2021 Dec 1;8:704501. doi: 10.3389/fcvm.2021.704501. eCollection 2021.
Both Niemann-Pick C1-like 1 (NPC1L1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) play a key role on dyslipidaemia. We aim to evaluate whether NPC1L1 and HMGCR genetic variants are associated with susceptibility of premature triple-vessel disease (PTVD). Four single-nucleotide polymorphisms (SNPs) (rs11763759, rs4720470, rs2072183, and rs2073547) of NPC1L1; and three SNPs (rs12916, rs2303151, and rs4629571) of HMGCR were genotyped in 872 PTVD patients (males ≤ 50 years old and females ≤ 60 years old), and 401 healthy controls. After adjusting for age and sex, rs12916 of HMGCR was associated with the risk of PTVD in dominance model [odds ratio (OR) = 1.68, 95% confidence intervals (CI): 1.29-2.18, < 0.001], recessive model (OR = 1.43, 95% CI: 1.08-1.90, = 0.013) and codominant model (OR = 1.38, 95% CI: 1.17-1.63, < 0.001); meanwhile, rs4720470 of NPC1L1 was related to increased risk of PTVD in recessive model (OR = 1.74, 95% CI: 1.14-2.74, = 0.013). Patients who carried both variant rs4720470 and rs12916 also had the risk of PTVD ( < 0.001); however, there were no correlation between these SNPs and the SNYTAX score (all > 0.05). This is the first report that rs4720470 is a novel polymorphism of the NPC1L1 gene associated with PTVD, and rs12916 of HMGCR gene appears to be a strong genetic marker of PTVD. Our study may improve the early warning, therapeutic strategies and drug development of PTVD.
尼曼-匹克C1样蛋白1（NPC1L1）和3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）在血脂异常中均起关键作用。我们旨在评估NPC1L1和HMGCR基因变异是否与早发三支血管病变（PTVD）的易感性相关。对872例PTVD患者（男性≤50岁，女性≤60岁）和401例健康对照者进行了NPC1L1的4个单核苷酸多态性（SNP）（rs11763759、rs4720470、rs2072183和rs2073547）以及HMGCR的3个SNP（rs12916、rs2303151和rs4629571）的基因分型。在调整年龄和性别后，HMGCR的rs12916在显性模型[优势比（OR）=1.68，95%置信区间（CI）：1.29 - 2.18，P<0.001]、隐性模型（OR = 1.43，95%CI：1.08 - 1.90，P = 0.013）和共显性模型（OR = 1.38，95%CI：1.17 - 1.63，P<0.001）中与PTVD风险相关；同时，NPC1L1的rs4720470在隐性模型中与PTVD风险增加相关（OR = 1.74，95%CI：1.14 - 2.74，P = 0.013）。携带rs4720470和rs12916变异的患者也有PTVD风险（P<0.001）；然而，这些SNP与SYNTAX评分之间无相关性（均P>0.05）。这是首次报道rs4720470是与PTVD相关的NPC1L1基因的新型多态性，HMGCR基因的rs12916似乎是PTVD的强遗传标记。我们的研究可能会改善PTVD的早期预警、治疗策略和药物研发。
