Clinical Core Laboratory, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, People's Republic of China.
Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, 514031, People's Republic of China.
BMC Cardiovasc Disord. 2020 Mar 11;20(1):127. doi: 10.1186/s12872-020-01410-7.
Acute coronary syndrome (ACS) is the most serious type of coronary heart disease and is a global medical burden. The pathogenesis of ACS is very complex and still poorly understood. Epidemiologic studies have revealed that the manifestation of ACS are the results of the interactions between multiple environmental and genetic factors. The present study aimed to investigate the role of polymorphisms of MTHFR C677T and ALDH2 Glu504Lys as risk factors for ACS in a Hakka population in southern China.
Between September 1, 2015 and October 31, 2017, a total of 1957 individuals, including 860 ACS patients and 1097 controls were recruited. Blood samples were collected and genotypes were determined by DNA microarray chip method and direct sequencing method.
For the MTHFR C677T polymorphism, frequencies of CC, CT, and TT genotypes were 53.60% versus 55.33, 39.53% versus 38.65 and 6.86% versus 6.02% in patients with ACS versus controls, respectively(p > 0.05). The differences in genotype frequencies between the ACS patients and controls in the three genetic model were not statistically significant. For the ALDH2 Glu504Lys polymorphism, the frequencies of ALDH211, ALDH212, and ALDH222 genotypes were 48.72, 42.67 and 8.6% in the ACS patients, respectively, while these were 53.33, 39.11 and 7.57% in the controls, respectively, showing no significant difference in the distribution of the ALDH2 genotype between the groups. Using the wild genotype ALDH211 as reference, relative risk analysis revealed a slightly increased risk for ACS in individuals with the ALDH212 plus ALDH222 genotypes (odds ratio (OR) = 1.203, 95% confidence interval (CI) = 1.006-1.438, p = 0.043). In a multivariate logistic regression model, even after adjusting for potential covariates, the association between ALDH2 *2 allele and ACS remained significant (OR = 1.242, 95% CI = 1.045-1.561, p = 0.038).
We present findings regarding the possible clinical impact of the ALDH2*2 variant on ACS patients in a Hakka population in southern China and our findings might help to stratify the high-risk ACS patients and implement appropriate strategies for this genetic subpopulation to ultimately guide the precision preventive procedures in the future.
急性冠状动脉综合征（ACS）是最严重的冠心病类型，是全球的医疗负担。ACS 的发病机制非常复杂，目前仍知之甚少。流行病学研究表明，ACS 的表现是多种环境和遗传因素相互作用的结果。本研究旨在探讨 MTHFR C677T 和 ALDH2 Glu504Lys 多态性作为中国南方客家人群 ACS 危险因素的作用。
2015 年 9 月 1 日至 2017 年 10 月 31 日，共纳入 1957 例患者，包括 860 例 ACS 患者和 1097 例对照。采集血样，采用 DNA 微阵列芯片法和直接测序法检测基因型。
对于 MTHFR C677T 多态性，ACS 患者与对照组 CC、CT 和 TT 基因型的频率分别为 53.60%、55.33%、39.53%和 6.86%（p>0.05）。三种遗传模型中 ACS 患者与对照组之间基因型频率的差异无统计学意义。对于 ALDH2 Glu504Lys 多态性，ACS 患者中 ALDH211、ALDH212 和 ALDH222 基因型的频率分别为 48.72%、42.67%和 8.6%，对照组中分别为 53.33%、39.11%和 7.57%，两组间 ALDH2 基因型分布无显著性差异。以野生基因型 ALDH211 为参照，相对风险分析显示，ALDH212 加 ALDH222 基因型的 ACS 风险略有增加（比值比（OR）=1.203，95%置信区间（CI）=1.006-1.438，p=0.043）。在多变量 logistic 回归模型中，即使调整了潜在的混杂因素，ALDH2*2 等位基因与 ACS 之间的关联仍然显著（OR=1.242，95%CI=1.045-1.561，p=0.038）。
我们在南方客家人群中发现了 ALDH2*2 变异可能对 ACS 患者的临床影响的证据，我们的发现可能有助于对高危 ACS 患者进行分层，并为这一遗传亚群实施适当的策略，最终指导未来的精准预防措施。
