Aldehyde Dehydrogenase 2 Rs671 Polymorphism Research Articles

The role of ALDH2 rs671 polymorphism and C-reactive protein in the phenotypes of male ALS patients.

The aldehyde dehydrogenase 2 (ALDH2) rs671 (A) allele has been implicated in neurodegeneration, potentially through oxidative and inflammatory pathways. The study aims to investigate the effects of the ALDH2 rs671 (A) allele and high sensitivity C-reactive protein (hs-CRP) on the clinical phenotypes of amyotrophic lateral sclerosis (ALS) in male and female patients. Clinical data and ALDH2 rs671 genotype of 143 ALS patients, including 85 males and 58 females, were collected from January 2018 to December 2022. All patients underwent assessment using the Chinese version of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Complete blood count and metabolic profiles were measured. Clinical and laboratory parameters were compared between carriers and non-carriers of the rs671 (A) allele in males and females, respectively. The significant parameters and rs671 (A) Allele were included in multivariate linear regression models to identify potential contributors to motor and cognitive impairment. Mediation analysis was employed to evaluate any mediation effects. Male patients carrying rs671 (A) allele exhibited higher levels of hs-CRP than non-carriers (1.70 mg/L vs. 0.50 mg/L, p = 0.006). The rs671 (A) allele was identified as an independent risk factor for faster disease progression only in male patients (β = 0.274, 95% CI = 0.048-0.499, p = 0.018). The effect of the rs671 (A) allele on the executive function in male patients was fully mediated by hs-CRP (Indirect effect = -1.790, 95% CI = -4.555--0.225). No effects of the rs671 (A) allele or hs-CRP were observed in female ALS patients. The effects of the ALDH2 rs671 (A) allele and the mediating role of hs-CRP in male patients remained significant in the sensitivity analyses. The ALDH2 rs671 (A) allele contributed to faster disease progression and hs-CRP mediated cognitive impairment in male ALS patients.

Aldehyde dehydrogenase 2 rs671 a/A Genotype is Associated with an Increased Risk of Early Onset Coronary Artery Stenosis.

The role of aldehyde dehydrogenase 2 (ALDH2) in cardiovascular diseases has been gradually studied. However, it is unclear whether ALDH2 polymorphism is associated with the risk of early onset (onset age ≤55 years old in men and ≤65 years old in women) coronary artery stenosis (CAS). The association between ALDH2 single nucleotide polymorphism (SNP) rs671 and risk in patients with early onset CAS was investigated in this study. The study included 213 early onset CAS patients and 352 individuals without CAS were set as controls. The ALDH2 rs671 polymorphism was genotyped by polymerase chain reaction (PCR) - microarray. Differences in ALDH2 rs671 genotypes and alleles between patients and controls were compared. Multiple logistic regression analysis was performed after adjusting for gender, body mass index (BMI), smoking history, drinking history, and diabetes mellitus to assess the relationship between ALDH2 rs671 genotypes and early onset CAS risk. The frequency of the ALDH2 rs671 G/G genotype was lower in the early onset CAS patients (43.7% vs 55.3%, p=0.007) than that in the controls. The frequency of the ALDH2 rs671 A allele was higher (32.9% vs 25.0%) than that in the controls (p=0.005). After adjusting for other confounding factors, multivariate logistic regression showed that ALDH2 rs671 A/A genotype (A/A vs G/G: odds ratio (OR) 2.508, 95% confidence interval (CI): 1.130-5.569, p=0.024), overweight (BMI≥24.0 vs 18.5-23.9: OR 5.047, 95% CI: 3.275-7.777, p<0.001), history of smoking (yes vs no: OR 2.813, 95% CI: 1.595-4.961, p<0.001), and diabetes mellitus (yes vs no: OR 2.191, 95% CI: 1.397-3.437, p=0.001) were the independent risk factors of early onset CAS. In men ≤55 years old and women ≤65 years old, individuals with ALDH2 rs671 A/A genotype, overweight (BMI ≥24.0 kg/m2), smoking history, and diabetes mellitus increased risk of developing CAS.

Aldehyde Dehydrogenase 2 rs671 G/A and a/A Genotypes are Associated with the Risk of Acute Myocardial Infarction.

Aldehyde dehydrogenase 2 (ALDH2) is a key catalytic enzyme involved in the aldehyde metabolism that plays an important role in the occurrence and development of acute myocardial infarction (AMI). However, the relationship of ALDH2 polymorphism and susceptibility to AMI may differ among different regions and populations, and it has not yet been reported in Hakka population. The purpose of the present study was to investigate it in this population. Four hundred and nineteen AMI patients and 636 individuals without AMI were included in the present study. The ALDH2 rs671 polymorphism was genotyped using polymerase chain reaction (PCR)-microarray. Differences in ALDH2 rs671 genotypes and alleles between patients and controls were compared, and the relationship between ALDH2 rs671 genotypes and AMI risk was analyzed. Patients with AMI had a lower frequency of ALDH2 rs671 G/G genotype (43.2% vs 52.7%, p=0.003), and a higher G/A genotype (45.6% vs 38.5%, p=0.025) than controls. And AMI patients had a lower frequency of ALDH2 rs671 G allele (66.0% vs 71.9%), and a higher A allele (34.0% vs 28.1%) (p=0.004) than controls. Logistic regression analysis showed that overweight (body mass index (BMI)≥24.0 kg/m2 vs BMI 18.5-23.9 kg/m2: odds ratio (OR) 2.046, 95% confidence interval (CI): 1.520-2.754, p<0.001), history of hypertension (yes vs no: OR 3.464, 95% CI: 2.515-4.770, p<0.001), ALDH2 rs671 G/A genotype (G/A vs G/G: OR 1.476, 95% CI: 1.102-1.976, p=0.009), and A/A genotype (A/A vs G/G: OR 1.656, 95% CI: 1.027-2.668, p=0.038) maybe the independent risk factors for AMI. Overweight (BMI≥24.0 kg/m2), a history of hypertension, and ALDH2 rs671 G/A or A/A genotypes increased the risk of developing AMI in Hakka population.

ALDH2 deficiency exacerbates MCD-diet induced MASLD by modulating bile acid metabolism

Aldehyde dehydrogenase 2 (ALDH2), an acetaldehyde dehydrogenase in mitochondria, is primarily responsible for metabolizing alcohol-derived acetaldehyde and other endogenous aldehydes. Inactivating ALDH2 rs671 polymorphism is found in up to 8 % of the global population and 40 % of the East Asian population. Recent studies have shown that rs671 SNP mutation in the human ALDH2 gene is associated with an increased risk of metabolic dysfunction-associated steatotic liver diseases (MASLD), but the mechanism remains unclear. Here, we identify the role of ALDH2 in MASLD. Firstly, ALDH2 activity was lower in MASLD patients and the methionine-choline deficiency (MCD) diet induced MASLD model. Secondly, activation of ALDH2 activity with Alda-1 (ALDH2 agonist) attenuated MCD-diet induced hepatic triglyceride (TG) accumulation and steatosis, whereas the opposite result was observed with cyanamide (CYA, ALDH2 inhibitor). Furthermore, ALDH2 deficiency exacerbated hepatic steatosis, inflammation, and fibrosis in the MCD-diet induced mice. RNA sequencing (RNA-seq) revealed that oxysterol 7-α hydroxylase (Cyp7b1) and the related metabolic pathway significantly changed in the MCD-diet challenged ALDH2−/− mice. In ALDH2−/− mice, the expression of Cyp7b1 was downregulated and FXR/SHP signaling was inhibited, reducing the alternative bile acid (BA) synthetic pathway. In our in vitro experiments, knockdown of ALDH2 exacerbated TG accumulation in hepatocytes, whereas the opposite result was observed with overexpression of ALDH2. Moreover, chenodeoxycholic acid (CDCA) rescued ALDH2 downregulation induced TG accumulation in hepatocytes. Our study reveals that ALDH2 attenuates hepatocyte steatosis by regulating the alternative BA synthesis pathway, and ALDH2 may serve as a potential target for the treatment of MASLD.

Changes of neurofilament light chain in patients with alcohol dependence following withdrawal and the genetic effect from ALDH2 Polymorphism.

Neurofilament light chain (NFL), as a measure of neuroaxonal injury, has recently gained attention in alcohol dependence (AD). Aldehyde dehydrogenase 2 (ALDH2) is the major enzyme which metabolizes the alcohol breakdown product acetaldehyde. An ALDH2 single nucleotide polymorphism (rs671) is associated with less ALDH2 enzyme activity and increased neurotoxicity. We examined the blood NFL levels in 147 patients with AD and 114 healthy controls using enzyme-linked immunosorbent assay and genotyped rs671. We also followed NFL level, alcohol craving and psychological symptoms in patients with AD after 1 and 2weeks of detoxification. We found the baseline NFL level was significantly higher in patients with AD than in controls (mean ± SD: 264.2 ± 261.8 vs. 72.1 ± 35.6pg/mL, p < 0.001). The receiver operating characteristic curve revealed that NFL concentration could discriminate patients with AD from controls (area under the curve: 0.85; p < 0.001). The NFL levels were significantly reduced following 1 and 2weeks of detoxification, with the extent of reduction correlated with the improvement of craving, depression, and anxiety (p < 0.001). Carriers with the rs671 GA genotype, which is associated with less ALDH2 activity, had higher NLF levels either at baseline or after detoxification compared with GG carriers. In conclusion, plasma NFL level was increased in patients with AD and reduced after early abstinence. Reduction in NFL level corroborated well with the improvement of clinical symptoms. The ALDH2 rs671 polymorphism may play a role in modulating the extent of neuroaxonal injury and its recovery.

ALDH2 rs671 Polymorphism Likely a Risk Factor for Hemorrhagic Stroke: A Hospital-Based Study.

Hypertension is the main risk factor for hemorrhagic stroke. Aldehyde dehydrogenase 2 (ALDH2) may inhibit the occurrence of hypertension by anti-oxidative stress and vascular dilation. The purpose was to investigate the relationship of ALDH2 polymorphisms with hemorrhagic stroke in Hakka Chinese. A total of 329 patients with hemorrhagic stroke and 515 controls were enrolled, and medical records (smoking and drinking history, hypertension, and diabetes) were collected. The genotypes of ALDH2 rs671 of the two groups were detected and analyzed. The proportion of the ALDH2 rs671 G/G, G/A, and A/A genotype in patients with hemorrhagic stroke was 55.9%, 37.4%, and 6.7%, respectively, while those were 65.0%, 30.7%, and 4.3% in controls, respectively. There was statistically significant difference in ALDH2 rs671 genotypes distribution (P=0.021) and alleles distribution (P=0.005) between patients and controls. Among hemorrhagic stroke patients, no statistically significant differences were observed between patients with ALDH2 different genotypes. Logistic regression analysis showed that there was significantly high risk of hemorrhagic stroke in men (male vs female: adjusted OR 1.711, 95% CI 1.154-2.538, P=0.008), the presence of hypertension (with vs without hypertension: adjusted OR 16.095, 95% CI 10.958-23.641, P<0.001), and the presence of ALDH2 rs671 G/A genotype (G/A vs G/G: adjusted OR 1.679, 95% CI 1.151-2.450, P=0.007) or A/A genotype (A/A vs G/G: adjusted OR 2.516, 95% CI 1.132-5.591, P=0.024). ALDH2 rs671 polymorphism likely a risk factor for hemorrhagic stroke.

The role of aldehyde dehydrogenase 2 in cardiovascular disease.

Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme involved in the detoxification of alcohol-derived acetaldehyde and endogenous aldehydes. The inactivating ALDH2 rs671 polymorphism, present in up to 8% of the global population and in up to 50% of the East Asian population, is associated with increased risk of cardiovascular conditions such as coronary artery disease, alcohol-induced cardiac dysfunction, pulmonary arterial hypertension, heart failure and drug-induced cardiotoxicity. Although numerous studies have attributed an accumulation of aldehydes (secondary to alcohol consumption, ischaemia or elevated oxidative stress) to an increased risk of cardiovascular disease (CVD), this accumulation alone does not explain the emerging protective role of ALDH2 rs671 against ageing-related cardiac dysfunction and the development of aortic aneurysm or dissection. ALDH2 can also modulate risk factors associated with atherosclerosis, such as cholesterol biosynthesis and HDL biogenesis in hepatocytes and foam cell formation and efferocytosis in macrophages, via non-enzymatic pathways. In this Review, we summarize the basic biology and the clinical relevance of the enzymatic and non-enzymatic, tissue-specific roles of ALDH2 in CVD, and discuss the future directions in the research and development of therapeutic strategies targeting ALDH2. A thorough understanding of the complex roles of ALDH2 in CVD will improve the diagnosis, management and prognosis of patients with CVD whoharbour the ALDH2 rs671 polymorphism.

The Association between the ALDH2 rs671 Polymorphism and Athletic Performance in Japanese Power and Strength Athletes.

The rs671 polymorphism is associated with the enzymatic activity of aldehyde dehydrogenase 2 (ALDH2), which is weakened by the A allele in East Asians. We recently reported the association of this polymorphism with the athletic status in athletic cohorts and the muscle strength of non-athletic cohorts. Therefore, we hypothesized the association of ALDH2 rs671 polymorphism with the performance in power/strength athletes. We aimed to clarify the relationship between the ALDH2 rs671 polymorphism and performance in power/strength athletes. Participants comprising 253 power/strength athletes (167 men and 86 women) and 721 healthy controls (303 men and 418 women) were investigated. The power/strength athletes were divided into classic powerlifting (n = 84) and weightlifting (n = 169). No differences in the genotypes and allele frequencies of the ALDH2 rs671 polymorphism and an association between performance and the ALDH2 rs671 genotype were observed in weightlifters. However, the relative values per body weight of the total record were lower in powerlifters with the GA + AA genotype than those with the GG genotype (7.1 ± 1.2 vs. 7.8 ± 1.0; p = 0.010, partial η2 = 0.08). Our results collectively indicate a role of the ALDH2 rs671 polymorphism in strength performance in powerlifters.

Aldehyde dehydrogenase 2 and arrhythmogenesis.

Cardiac arrhythmia is a common cardiovascular disease that leads to considerable economic burdens and significant global public health challenges. Despite the remarkable progress made in recent decades, antiarrhythmic therapy remains suboptimal. Aldehyde dehydrogenase 2 (ALDH2), a critical detoxifying enzyme, catalyzes toxic aldehydes and protects individuals from damage caused by oxidative stress. Accumulating evidence has demonstrated that ALDH2 activation has potential antiarrhythmic benefits. The correlation between ALDH2 deficiency and arrhythmogenesis has been widely recognized. In this review, we summarize recent research on the potential role of ALDH2 activation and antiarrhythmic protection, as well as the role played by the ALDH2∗2 polymorphism (rs671) in promoting arrhythmic risk. Additionally, we discuss important new findings illustrating the use of ALDH2 activators, which may prove to be promising antiarrhythmic therapy agents.

The ALDH2 rs671 polymorphism is associated with athletic status and muscle strength in a Japanese population.

Aldehyde dehydrogenase 2 (ALDH2) catalyses aldehyde species, including alcohol metabolites, mainly in the liver. We recently observed that ALDH2 is also expressed in skeletal muscle mitochondria; thus, we hypothesize that rs671 polymorphism-promoted functional loss of ALDH2 may induce deleterious effects in human skeletal muscle. We aimed to clarify the association of the ALDH2 rs671 polymorphism with muscle phenotypes and athletic capacity in a large Japanese cohort. A total of 3,055 subjects, comprising 1,714 athletes and 1,341 healthy control subjects (non-athletes), participated in this study. Non-athletes completed a questionnaire regarding their exercise habits, and were subjected to grip strength, 30-s chair stand, and 8-ft walking tests to assess muscle function. The ALDH2 GG, GA, and AA genotypes were detected at a frequency of 56%, 37%, and 7% among athletes, and of 54%, 37%, and 9% among non-athletes, respectively. The minor allele frequency was 25% in athletes and 28% in controls. Notably, ALDH2 genotype frequencies differed significantly between athletes and non-athletes (genotype: p = 0.048, allele: p = 0.021), with the AA genotype occurring at a significantly lower frequency among mixed-event athletes compared to non-athletes (p = 0.010). Furthermore, non-athletes who harboured GG and GA genotypes exhibited better muscle strength than those who carried the AA genotype (after adjustments for age, sex, body mass index, and exercise habits). The AA genotype and A allele of the ALDH2 rs671 polymorphism were associated with a reduced athletic capacity and poorer muscle phenotypes in the analysed Japanese cohort; thus, impaired ALDH2 activity may attenuate muscle function.

Causal Association Between Alcohol Consumption and Atrial Fibrillation: A Mendelian Randomization Study.

Previous observational studies presented a positive association between alcohol and atrial fibrillation (AF). However, previous studies using genetic polymorphisms on the causal relationship between alcohol consumption and AF have reported conflicting results. This study aimed to evaluate the causality between alcohol consumption and AF using the aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism, which is the genetic variant with the most potent effect on drinking behavior. A total of 8,964 participants from the Dong-gu Study were included in the present study. The causal association between alcohol consumption and AF was evaluated through a Mendelian randomization (MR) analysis using the ALDH2 rs671 polymorphism as an instrumental variable. No significant relationship between alcohol consumption and AF was found in the observational analysis. However, the genetic analysis using the ALDH2 polymorphism showed a significant association in men. In the MR analysis, genetically predicted daily alcohol consumption was positively related to AF. MR analysis revealed a significant association between the amount of alcohol consumption and AF, which suggests that the association may be causal.

Alcohol consumption, aldehyde dehydrogenase 2 gene rs671 polymorphism, and psoriasis in Taiwan

Background: Although alcohol use has been determined as a predisposing factor for psoriasis, research findings have been inconsistent. Objectives: This study investigated whether alcohol intake is causally linked to psoriasis. Methods: The presence of rs671 polymorphism in the aldehyde dehydrogenase 2 (ALDH2) gene was investigated in 258 psoriasis patients and 605 healthy controls. The rs671 was employed as an instrumental variable for predicting alcohol use. Mendelian randomization (MR) was utilized to assess the causality between genetically determined alcohol consumption and psoriasis using the two-stage least-square (2SLS) approach. A replication study of MR analysis with inverse-variance weighting (IVW), MR-Egger regression, and weighted median methods was performed using openly accessible alcohol consumption and psoriasis summary statistics from the UK Biobank. Results: Between psoriasis and controls, there were no significant differences in genotype and allele frequencies for the ALDH2 rs671 polymorphism. The G allele of the rs671 was positively linked with alcohol intake. The ALDH2 rs671 genetically determined alcohol intake was not linked to the risk of psoriasis in the 2SLS analysis (β = −0.011, P = 0.960). The MR replication study also found no evidence of genetic propensity to greater alcohol consumption increasing the risk of psoriasis (β = −0.00065, P = 0.6002 in IVW; β = −0.00099, P = 0.6851 in MR-Egger; and β = −0.00181, P = 0.3558 in weighted median analysis). Conclusion: ALDH2 rs671 may not have a role in psoriasis susceptibility in Taiwanese. The MR analysis found no causality between alcohol consumption and psoriasis.

Cortical thickness is differently associated with ALDH2 rs671 polymorphism according to level of amyloid deposition

Accumulating evidence indicates that amyloid-beta (Aβ) deposition and biogenic aldehyde accumulation contribute to the pathogenesis of neurodegenerative diseases. Human aldehyde dehydrogenase 2 (ALDH2) metabolizes biogenic aldehydes produced in the brain to prevent damage. However, r671G>A, a single nucleotide polymorphism of ALDH2, causes aldehyde accumulation and decreased ALDH2 activity. We aimed to investigate whether Aβ deposition and rs671 polymorphism have an interaction effect on cortical thickness (CTh). We grouped 179 participants in the Biobank Innovations for chronic Cerebrovascular disease With ALZheimer's disease Study as follows: amyloid (–) [A(–)] and amyloid (+) [A(+)] groups based on the Aβ deposition degree; A-carrier (AC) and GG (GG) groups based on the presence/absence of the rs671 A allele; and their combinations, i.e., A(–)AC, A(–)GG, A(+)AC, and A(+)GG groups. A multiple regression analysis identified nine regions of interest. Compared with the A(–)GG group, the A(–)AC group showed thinner CTh in all regions. There were no significant differences between the A(+)AC and A(+)GG groups. We observed an interaction effect of amyloid deposition and rs671 polymorphism on CTh. The CTh in the A(–) group appeared to be strongly influenced by rs671 polymorphism, which could have contributed to cortical thinning and biogenic aldehyde accumulation in the AC group. Additionally, CTh in the A(+) group appeared to be strongly influenced by amyloid deposition.

Analysis of gender-specific associations between aldehyde dehydrogenase 2 (ALDH2) rs671 genetic polymorphisms and serum uric acid levels in Han Chinese.

BackgroundSerum uric acid (SUA) is influenced by lifestyle and genetics, and unbalanced SUA levels are linked to various common disorders. While the aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism appears to be associated with SUA levels, the evidence remains inconclusive. The aim of this study was to examine the distribution of the ALDH2 rs671 polymorphism among Han Chinese in Beijing and determine the association between this polymorphism and SUA.MethodsA total of 6,461 randomized healthy individuals were included in the study. Biochemical indicators were tested and ALDH2 rs671 polymorphism testing was conducted for subjects enrolled in the study. The distribution of the ALDH2 rs671 polymorphism and the relationship between genotype and the levels of serum lipids and uric acid (UA) were analyzed.ResultsThe ALDH2 rs671 genotype frequencies were 68.1% (G/G), 29.3% (G/A), and 2.6% (A/A). There was no significant difference in allele distribution between males and females. In males, different ALDH2 genotypes exhibited significant differences in several biochemical analytes, including body mass index (BMI), blood glucose (Glu), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), UA, glutamyl transpeptidase (GGT), and creatinine (Cr) (P<0.05). No such differences were found in females. SUA levels in G/A and A/A-carrying males were significantly lower than those of G/G-carrying males. The effect of the ALDH2 polymorphism on UA was still significant after further adjustment for factors including BMI, Glu, TC, HDL-C, Cr, and GGT.ConclusionsThe ALDH2 polymorphism is related to SUA in Beijing males, and A allele-carrying males have lower SUA levels.

Association between Alcohol Consumption and Serum Cortisol Levels: a Mendelian Randomization Study.

BackgroundSeveral studies have reported conflicting results regarding the relationship between alcohol consumption and cortisol levels. However, the causality between alcohol consumption and cortisol levels has not been evaluated.MethodsThis study examined 8,922 participants from the Dong-gu Study. The aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism was used as an instrumental variable for alcohol consumption. The association between the genetically predicted alcohol consumption and cortisol level was evaluated with Mendelian randomization (MR) using two-stage least squares regression.ResultsAlcohol consumption was positively associated with the serum cortisol level in both sexes in the observational analysis. In the MR analysis, the genetically predicted alcohol consumption was positively related to the cortisol level in men, with cortisol levels increasing by 0.18 µg/dL per drink per day. However, there was no relationship in women in the MR analysis.ConclusionThe predicted alcohol consumption according to the ALDH2 rs671 polymorphism was positively related to the cortisol levels, suggesting a causal relationship between alcohol consumption and cortisol levels.

Alcohol consumption is associated with glaucoma severity regardless of ALDH2 polymorphism

The present study investigated the effect of aldehyde dehydrogenase2 (ALDH2) rs671 polymorphism and alcohol consumption on the severity of primary open-angle glaucoma (POAG). The questionnaire for alcohol consumption pattern and targeted genotyping for ALDH2 rs671 polymorphism was performed from 445 Korean POAG patients. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thicknesses were measured and compared according to alcohol consumption and ALDH2 rs671 genotype. Heavy drinking group eyes had thinner RNFL thickness than did abstinence group eyes (65.0 ± 10.9 vs. 70.9 ± 11.5 µm, P = 0.023). Both mild (65.8 ± 9.6 µm) and heavy (63.8 ± 8.4 µm) drinking group eyes had significantly thinner macular GCIPL thickness than did abstinence group eyes (68.1 ± 8.2 µm, P = 0.003). However, ALDH2 rs671 polymorphism did not show any significant association with RNFL or GCIPL thickness. Alcohol consumption was significantly associated with GCIPL thinning (β = –0.446, P = 0.035) after adjustment for multiple confounding factors. As excessive alcohol consumption was significantly associated with thinner GCIPL thickness while ALDH2 polymorphism had no significant effect on RNFL or GCIPL thickness, glaucoma patients should avoid excessive alcohol consumption regardless of ALDH2 polymorphism.

Association between ALDH2 rs671 polymorphism and risk of ischemic stroke: A protocol for systematic review and meta analysis.

In last decades, many scholars have studied the relationship between aldehyde dehydrogenase 2 (ALDH2) rs671 and ischemic stroke (IS), however, the results obtained from these studies were inconclusive. The purpose of this study was to investigate the association between rs671 and the risk of IS by systematically review.Two researchers independently screened relevant published literatures, derived data and estimated the risk of bias of the research in Pubmed, Embase, Ovid, China National Knowledge Infrastructure (CNKI), Cochrane Library and China Biomedical Literature Database throughout March 29, 2020. All statistical analyses were performed with the Stata 12.0 software. The data of the study was analyzed using fixed and random effects models. The results were expressed by odds ratio (OR) and 95% confidence interval (95%CI).A total of 10 articles were included this study. The total number of samples for all studies was 5265, including 2762 cases and 2503 controls. Statistical results indicated statistical differences between ALDH2 rs671 polymorphism and IS under dominant model (AA vs. AG + GG) and allelic model (A vs G), ORs (95% CI) were 1.66 (1.27–2.17) (P = .00) and 1.34 (1.05–1.71) (P = .02), respectively. But there was no statistical difference under recessive model (AA + AG vs GG), OR (95% CI) was 1.40 (0.99–1.97), P = .06.ALDH2 rs671 polymorphism was related to IS risk for Chinese population and the A allele of rs671 may be a risk factor of IS.

ALDH2 Gene rs671 Polymorphism May Decrease the Risk of Essential Hypertension.

Aldehyde dehydrogenase-2 (ALDH2) rs671 G>A polymorphism can influence the activity of ALDH2 and may be associated with the risk of essential hypertension (EH). Although many previous studies have explored such a relationship, the conclusion is still controversial.The PubMed, Embase, and China National Knowledge Infrastructure databases were searched on the ALDH2 gene and EH. We used the Newcastle-Ottawa Scale to evaluate the quality of the study. Then we calculated the strength of relationship between ALDH2 rs671 mutation and EH by utilizing odds ratios and 95% confidence intervals. Besides, subgroup analysis and sensitivity analysis were performed and the publication bias was assessed.There were 12 studies containing 8153 cases and 10,162 controls. Our meta-analysis showed significant association between ALDH2 rs671 polymorphism and EH in four genetic models (the allele model, the homozygote model, the heterozygote model, and the dominant model), whereas it did not indicate this connection in the recessive model. However, a trend of decreased risk still could be seen. Furthermore, we also found an obvious association between rs671 mutation and the risk of EH in the male group than in the female group in all five genetic models.We concluded that ALDH2 rs671 G>A polymorphism may decrease the risk of EH. Furthermore, susceptibility to EH reduced in males but not in females. As a variant in ALDH2, rs671 G>A could be an attractive candidate for genetic therapy of EH. In addition, more case-control studies should be conducted to strengthen our conclusion and evaluate the gene-gene and gene-environment interactions between the ALDH2 gene and EH.

Association between ALDH2 Polymorphism and Gastric Cancer Risk in a Korean Population.

The association between alcohol and gastric cancer is stronger in East Asians than in other ethnic groups, presumably due to an aldehyde dehydrogenase 2 (ALDH2) polymorphism. Therefore, we investigated the relationship between the ALDH2 rs671 polymorphism and gastric cancer in a Korean population. This case-control study included 3,245 hospital patients newly diagnosed with gastric cancer and 8,732 population controls. The ALDH2 rs671 genotype was classified as inactive ALDH2 (GG) or active ALDH2 (GA/AA). The risk of gastric cancer was higher in men with the inactive ALDH2 than in those with active ALDH2 (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.09–1.39), whereas no significant association was found between ALDH2 genotype and gastric cancer in women (OR, 1.00; 95% CI, 0.99–1.02). In men, the association between ALDH2 genotype and gastric cancer was stronger in current drinkers. Our findings support the previously reported association between inactive ALDH2 and high risk of gastric cancer.

ALDH2 rs671 polymorphism and the risk of heart failure with preserved ejection fraction (HFpEF) in patients with cardiovascular diseases.

Aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism is an established genetic risk of hypertension, diabetes, and coronary heart diseases in Asian population. Previous experimental data showed ALDH2 regulated inflammation, a potential mechanism of heart failure with preserved ejection fraction (HFpEF). However, clinically, the association between ALDH2 polymorphism and incidence of HFpEF remains unknown. In this prospective cross-sectional study, ALDH2 genotyping was performed in 613 consecutive patients enrolled with cardiovascular diseases (CVDs), including hypertension, coronary heart diseases, and/or diabetes mellitus, with normal left ventricular ejection fraction (LVEF). HFpEF was diagnosed according to symptoms and/or signs of dyspnea, fatigue or ankle swelling, N-terminal pro-B-Type natriuretic peptide (NT pro-BNP ≥ 280 pg/mL), LVEF ≥ 50%, and at least one additional criterion: left atrial enlargement (left atrial diameter > 40 mm), diastolic dysfunction (E/E' ≥ 13 or E'/A' < 1) or concurrently with atrial fibrillation. Finally, of 613 patients with CVD, 379 patients (61.8%) were assigned to the wild-type ALDH2*1/*1 group and 234 patients (38.2%) to the mutation-type ALDH2*2 group according to genotyping results. Sixty-nine patients (11.3%) were diagnosed with HFpEF. In ALDH2*2 group, the occurrence of HFpEF was higher (15.4% vs. 8.7%, p = 0.011) than that in ALDH2*1/*1 group. Leukocyte count, the indicator of systemic inflammation, was significantly higher (6.9 ± 2.4 × 109/L vs. 6.5 ± 1.9 × 109/L, p = 0.010) in ALDH2*2 group compared to ALDH2*1/*1 group. In conclusion, ALDH2*2 variant is associated with the risk of HFpEF in patients with CVD. Increased systemic inflammation probably involved in this disease process.