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Aldehyde dehydrogenase 2 Glu504Lys variant predicts a worse prognosis of acute coronary syndrome patients.

ABSTRACT: Aldehyde dehydrogenase 2 (ALDH2) Glu504Lys variant was an independent risk factor for acute coronary syndrome (ACS). However, there are lacking researches about the relationship between the variant and prognosis of ACS. In the prospective study, 377 ACS patients were grouped into the wild-type (*1/*1) and the mutation (*2/*2 + *1/*2) groups according to genotype detection. Compared with the wild-type group, incidences of major adverse cardiac events (MACE) and cardiac death were both higher in the mutation group (9.2% vs 21.0%, P = .002; 5.2% vs 12.2%, P = .026); the MACE-free and the cardiac-death-free cumulative survival rates were obviously lower in the mutation group. Moreover, the mutant genotypes were associated with significantly increased risk of MACE and cardiac death (HR 2.443, 95%CI: 1.390-4.296, P = .002; HR 2.727, 95%CI: 1.303-5.708, P = .008). These results suggested that ALDH2 Glu504Lys variant could predict a worse prognosis of ACS patients.

SUBMITTER: Pan C

PROVIDER: S-EPMC5867093 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Aldehyde dehydrogenase 2 Glu504Lys variant predicts a worse prognosis of acute coronary syndrome patients.

Pan Chang C Zhao Yu Y Bian Yuan Y Shang Rui R Wang Jia-Li JL Xue Li L Wei Shu-Jian SJ Zhang He H Chen Yu-Guo YG Xu Feng F

Journal of cellular and molecular medicine 20180214 4

Aldehyde dehydrogenase 2 (ALDH2) Glu504Lys variant was an independent risk factor for acute coronary syndrome (ACS). However, there are lacking researches about the relationship between the variant and prognosis of ACS. In the prospective study, 377 ACS patients were grouped into the wild-type (*1/*1) and the mutation (*2/*2 + *1/*2) groups according to genotype detection. Compared with the wild-type group, incidences of major adverse cardiac events (MACE) and cardiac death were both higher in t ...[more]

PMID: 29441687

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Project description:BackgroundLactate dehydrogenase (LDH) is associated with the prognosis of many diseases, but the relationship between LDH and the poor prognosis (recurrence and death) of acute ischemic stroke (AIS) has not been fully clarified. This study aimed to investigate the association between admission LDH level and poor prognosis in patients with AIS.MethodsThis retrospective study enrolled AIS patients treated in Taizhou Hospital of Zhejiang Province from July 2019 to December 2019. Poor prognosis included AIS recurrence and all-cause death at 3, 6, and 18 months. The correction between LDH and poor prognosis or all-cause death was assessed. Lasso Cox expression and multivariate Cox expression analyses were used to evaluate the association of LDH with the risk of poor prognosis and all-cause death, respectively. A nomogram was constructed to evaluate the predictive Values of LDH for the poor prognosis and all-cause death of AIS.Results732 patients were included in the study. Multivariate analysis shows that admission LDH levels were significantly correlated with poor prognosis [odds ratio (OR),1.003; 95% confidence interval (95% CI), 1.001-1.005; P = 0.001] and all-cause death (OR, 1.005; 95% CI, 1.000-1.009; P = 0.031). The correlation analysis showed that admission LDH level was positively correlated with National Institutes of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) score. Time-dependent receiver operating characteristic (td-ROC) curves analysis showed that the AUC values of admission LDH level for predicting prognosis of AIS patients in 3-month, 6-month, 12-month and 18-month were 0.706 (95% CI, 0.604-0.810), 0.653 (95% CI, 0.583-0.723), 0.616 (95% CI, 0.556-60676) and 0.610 (95% CI, 0.552-0.680), respectively. And td-ROC also showed that the AUC values of admission LDH level for predicting all-cause death of AIS patients in 3-month, 6-month,12-month and 18-month were 0.861 (95% CI, 0.764-0.958), 0.824 (95% CI, 0.753-0.890), 0.726 (95% CI, 0.633-0.819) and 0.715 (95% CI, 0.622-0.807), respectively. The nomograms were constructed to create the predictive models of the poor prognosis and all-cause death of AIS.ConclusionHigher LDH levels are independently associated with poor prognosis and all-cause death of AIS.

Project description: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.

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Aldehyde dehydrogenase 2 Glu504Lys variant predicts a worse prognosis of acute coronary syndrome patients.

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Aldehyde dehydrogenase 2 Glu504Lys variant predicts a worse prognosis of acute coronary syndrome patients.

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