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Background  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.    Methods  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.    Results  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  ALDH2*1*1 ,  ALDH2*1*2 , and  ALDH2*2*2  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  ALDH2*1*1  as reference, relative risk analysis revealed a slightly increased risk for ACS in individuals with the  ALDH2*1*2  plus  ALDH2*2*2  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).    Conclusions  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.

The role of MTHFR C677T and ALDH2 Glu504Lys polymorphism in acute coronary syndrome in a Hakka population in southern China