背景:脑中风(CS)是中国的主要死亡原因,以及由可变的危险因素和遗传因素引起的复杂疾病。本研究旨在研究中国汉族人群中MMP3,MMP14和MMP25单核苷酸多态性(SNP)与CS风险的关系。
方法:本病例对照研究共招募1,348名汉族人。成功筛选了四个候选基因座,包括MMP3的rs520540A/G和rs679620T/C,MMP14的rs2236302G/C和MMP25的rs10431961T/C。通过logistic回归分析评估4个SNPs与CS风险的相关性。通过假阳性报告概率(FPRP)分析结果的机会或显著性。通过多因素降维(MDR)评估与CS风险相关的四个SNP之间的相互作用。
结果:MMP3中rs520540A/G和rs679620C/TSNP与等位基因CS风险相关,共显性,显性和对数累加模型。具有rs520540-A等位基因和rs679620-T等位基因的携带者的缺血性卒中风险明显低于具有G/G或C/C基因型的携带者。然而,rs520540-A等位基因和rs679620-T等位基因与出血性卒中的高风险相关。分层分析表明,这两个SNP与<55岁人群CS风险降低有关。不吸烟和不饮酒的参与者,rs679620SNP也降低了男性参与者的CS风险。尿酸的水平,高密度脂蛋白胆固醇,rs520540和rs679620不同基因型患者的嗜酸性粒细胞存在差异。MMP14rs2236302G/C或MMP25rs10431961T/C与CS之间没有统计学上的显着关联,即使在按卒中亚型进行分层后,年龄,所有遗传模型中的性别以及吸烟和饮酒条件。
结论:MMP3rs520540A/G和rs679620C/T多态性与中国汉族人群的CS风险相关,为CS的预防和诊断提供了有用的信息。
Cerebral stroke (CS) is the leading cause of death in China, and a complex disease caused by both alterable risk factors and genetic factors. This study intended to investigate the association of MMP3, MMP14, and MMP25 single nucleotide polymorphisms (SNPs) with CS risk in a Chinese Han population.
A total of 1,348 Han Chinese were recruited in this
case-control study. Four candidate loci including rs520540 A/G and rs679620 T/C of MMP3, rs2236302 G/C of MMP14, and rs10431961 T/C of MMP25 were successfully screened. The correlation between the four SNPs and CS risk was assessed by logistic regression analysis. The results were analyzed by false-positive report probability (FPRP) for chance or significance. The interactions between four SNPs associated with CS risk were assessed by multifactor dimensionality reduction (MDR).
rs520540 A/G and rs679620 C/T SNP in MMP3 were associated with risk of CS in allele, codominant, dominant and log-additive models. Ischemic stroke risk were significantly lower in carriers with rs520540-A allele and rs679620-T allele than those with G/G or C/C genotypes. However, rs520540-A allele and rs679620-T allele were associated with higher risk of hemorrhagic stroke. Stratified analysis showed that these two SNPs were associated with reduced risk of CS in aged < 55 years, non-smoking and non-drinking participants, and rs679620 SNP also reduced CS risk in male participants. The levels of uric acid, high-density lipoprotein cholesterol, and eosinophil were different among patients with different genotypes of rs520540 and rs679620. No statistically significant association was found between MMP14 rs2236302 G/C or MMP25 rs10431961 T/C with CS even after stratification by stroke subtypes, age, gender as well as smoking and drinking conditions in all the genetic models.
MMP3 rs520540 A/G and rs679620 C/T polymorphisms were associated with CS risk in the Chinese Han population, which provides useful information for the prevention and diagnosis of CS.