Genetic variations in circadian rhythm genes and susceptibility for myocardial infarction

Abstract Disruption of endogenous circadian rhythms has been shown to increase the risk of developing myocardial infarction (MI), suggesting that circadian genes might play a role in determining disease susceptibility. We conducted a case-control study on 200 patients hospitalized due to MI and 200 healthy controls, investigating the association between MI and single nucleotide polymorphisms (SNPs) in four circadian genes (ARNTL, CLOCK, CRY2, and PER2). The variants of all four genes were chosen based on their previously reported association with cardiovascular risk factors, which have a major influence on the occurrence of myocardial infarction. Statistically significant differences, assessed through Chi-square analysis, were found in genotype distribution between cases and controls of the PER2 gene rs35333999 (p=0.024) and the CRY2 gene rs2292912 (p=0.028); the corresponding unadjusted odds ratios, also significant, were respectively OR=0.49 (95% CI 0.26-0.91) and OR=0.32 (95% CI 0.11-0.89). Our data suggest that genetic variability in the CRY2 and PER2 genes might be associated with myocardial infarction.

摘要 内源性昼夜节律紊乱已被证实可升高心肌梗死（myocardial infarction, MI）的发病风险，提示昼夜节律基因或在疾病易感性的调控中发挥重要作用。本研究针对200例因心肌梗死住院的患者与200名健康对照开展病例对照研究，探究心肌梗死与4种昼夜节律基因（ARNTL、CLOCK、CRY2及PER2）的单核苷酸多态性（single nucleotide polymorphisms, SNPs）之间的关联。本研究选取的上述4种基因的变异位点，均基于既往报道的与心血管危险因素存在关联的变异，而此类危险因素对心肌梗死的发生具有关键影响。经卡方分析（Chi-square analysis）评估后发现，PER2基因rs35339999（p=0.024）与CRY2基因rs2292912（p=0.028）的基因型分布在病例组与对照组间存在统计学显著差异；对应的未校正比值比（odds ratios, OR）同样具有统计学意义，分别为OR=0.49（95%置信区间0.26~0.91）与OR=0.32（95%置信区间0.11~0.89）。本研究数据表明，CRY2与PER2基因的遗传变异可能与心肌梗死的发生存在关联。