Genetic polymorphism of ALDH2 in Indonesia’s Minang ethnic

Background: In some people, acetaldehyde, a toxic product from ethanol oxidation, cannot be oxidized to acetate. The excess of acetaldehyde could cause facial flushing, dizziness, and hypertension when they consume ethanol. This ethanol sensitivity is caused by a deficiency of ALDH2. Objective: This study aims to analyze and count the polymorphism frequency of the ALDH2 gene in Indonesia’s Minang ethnic. Methods: DNA samples were taken randomly from hair bulbous of 60 subjects (male and female, 3rd generation). A nested polymerase chain reaction was conducted to amplify the ALDH2 in the samples. Afterward, restriction fragment length polymorphism (RFLP) was conducted to the amplicons using the EcoRI restriction enzyme. The measured parameters were the distribution of the wildtype, atypical homozygote, and heterozygote. Results: Results showed that out of 60 subjects, 53.33% have an atypical homozygote gene (subjects prone to hypersensitive to alcohol), 28.33% have a heterozygote gene, and 18.33% have a wildtype gene. The frequency of the atypical alleles in Minang ethnic is 0.675. Conclusion: The atypical ALDH2 allele was much higher than the normal ALDH2 allele, in which most participants have atypical homozygote ALDH2, suggesting the samples are sensitive to alcohol.

Alleles Frequency and Polymorphic Genes Genotypes Associated with Alcoholism in Kazakh Population

Background: There is a category of people with a congenial predisposition to alcohol abuse among the total population. The identification of such persons by molecular genetic diagnostics and the implementation of appropriate preventive measures can significantly reduce the incidence of alcoholism. Objectives: This research aimed to study the genetic foundations of alcohol dependence development in Kazakhs based on the analysis of population frequencies of polymorphic variants of predisposition to alcoholism genes. Materials and Methods: The material for the research was the DNA recovered from the peripheral blood of the recruited control group population, which was represented by 1,800 conditionally healthy individuals of Kazakh nationality. Isolated DNA samples were genotyped by PCR. Conclusions: Kazakhs take an intermediate position between the previously studied European and Asian populations by allele frequencies of nine polymorphic variants of ADH1B (rs2066701, rs1789891), ADH1C (rs1693425, rs698), HTR2C (rs6318), ALDH2 (rs671), CADM2 (rs9841829), KLB (rs11940694), DRD2 (rs1076560) genes. Possible markers of an increased risk of alcoholism development in Kazakhs are G alleles of polymorphic loci rs2066701 of the ADH1B gene and rs671 of the ALDH2 gene, and the protective effect is possible in the presence of A alleles rs2066701 of the ADH1B gene and rs671 of the ALDH2 gene.

Exploring ALDH2 Expression and Its Immune Infiltration in HNSC and Its Prognositic Correlation With Gender or Alcohol Intake

Aldehyde dehydrogenase 2 (ALDH2) point mutation ALDH2*2 is the common frequent human gene variant, espically in East Asians. However, nothing is known about their expression and mechanism of action in HNSC. This research tried to explore the clinical significance and immune characteristics of ALDH2 in HNSC. The receiver operating characteristic (ROC) curve was analysed to assessment the diagnostic value of ALDH2 expression. ALDH2 expression in normal tissues and HNSC tissues were evaluated by IHC. Also we analyzed ALDH2 gene expression in 4 HNSC cell lines. ALDH2 expression was significantly reduced in HNSC tissues (p< 0.05). HNSC patients with highly expressed ALDH2 have a better prognosis (p< 0.05). Then, GSEA analysis result pointed that these gene sets were connected with signaling pathways including JAK-STAT signaling pathway. We unexpectedly found a significant prognostic effect of ALDH2 in alcohol consumption and male HNSC patients. The correlation between ALDH2 expression and immunoinhibitors showed a effect for ALDH2 in modifying tumor immunology in HNSC and there may be a possible mechanism by which ALDH2 regulates functions of T cell in HNSC. We developed a nomogram prognostic model for HNSC patients. Moreover, low ALDH2 expression was a poor prognostic factor in male alcoholics of HNSC.

Origin and Spread of the ALDH2 Glu504Lys Allele

Gene polymorphism of acetaldehyde dehydrogenase 2 (ALDH2), a key enzyme for alcohol metabolism in humans, can affect catalytic activity. The ALDH2 Glu504Lys mutant allele has a high-frequency distribution in East Asian populations and has been demonstrated to be associated with an increased risk of cardiovascular disease, stroke, and tumors. Available evidence suggests that the evolution of the ALDH2 gene has been influenced by multiple factors. Random mutations produce Glu504Lys, and genetic drift alters the frequency of this allele; additionally, environmental factors such as hepatitis B virus infection and high-elevation hypoxia affect its frequency through selective effects, ultimately resulting in a high frequency of this allele in East Asian populations. Here, the origin, selection, and spread of the ALDH2 Glu504Lys allele are discussed, and an outlook for further research is proposed to realize a precision medical strategy based on the genetic and environmental variations in ALDH2.

Impact of ALDH2 Gene Polymorphism on Coronary Artery lesions in Ethnic Hakka Population with Acute Myocardial Infarction

Background: Aldehyde dehydrogenase 2 (ALDH2) contributes to converting acetaldehyde into acetate, thus plays a key role in the ethanol metabolism and oxidation of acetaldehyde. The aim of this study is to investigate the impact of Aldehyde dehydrogenase 2 (ALDH2) gene polymorphism on coronary artery lesions in ethnic Hakka patients with acute myocardial infarction (AMI). Methods: A total of 312 patients (male = 241, female = 71) with acute myocardial infarction (AMI) suffered ≥ 50% stenosis of at least one major coronary artery were recruited into the study. Lesions of AMI patients carried different ALDH2 genotypes were analyzed. Results: The incidence of multivessel lesions was higher in the ALDH2 mutation group (90.6%) than the ALDH2 wild group (80.3%) with reaching statistical significance (p = 0.009). Compare to the single lesion group, multivessel lesions group were more likely to be lower DBP (77.3 ± 14.1 versus 86.4 ± 13.8, p = 0.004), older (66.1 ± 12.2 versus 59 ± 12.1, p = 0.009), have hypertension (55.7% versus 30.8%, p = 0.023) in the ALDH2 wild patients. In the ALDH2 mutation patients, multivessel lesions group also tend to be elderly (65.9 ± 11.3 versus 58.5 ± 11.3, p = 0.011). In the addition, the multivessel lesions group presented higher levels of the TG and lower levels of the LDL-C than the single lesion group, but it is no statistical differences. The logistics regression showed that age and ALDH2 mutation were vulnerable to the multivessel lesions the ethnic Hakka population with AMI. Conclusions: The AMI patients in ethnic Hakka population carrying mutated ALDH2 allele was vulnerable to multiple coronary artery lesions. ALDH2 allele was associated with multiple coronary artery lesions in AMI patients among ethnic Hakka population. Key words: ALDH2 mutated allele, coronary artery lesions, acute myocardial infarction

Association between ALDH2 Gene Polymorphism and Late-onset Alzheimer Disease: An Up-to-date Meta-analysis

Objectives: Previous case-control studies have focused on the relationship between ALDH2 gene polymorphism and late-onset Alzheimer's Disease (LOAD), but no definite unified conclusion has been reached. Therefore, the correlation between ALDH2 Glu504Lys polymorphism and LOAD remains controversial. To analyze the correlation between ALDH2 polymorphism and the risk of LOAD, we implemented this up-to-date meta-analysis to assess the probable association. Methods: Studies were searched through China National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals, China Biology Medicine, PubMed, Cochrane Library, Clinical- Trials.gov, Embase, and MEDLINE from January 1, 1994 to December 31, 2018, without any restrictions on language and ethnicity. Results: Five studies of 1057 LOAD patients and 1136 healthy controls met our criteria for the analysis. Statistically, the ALDH2 GA/AA genotype was not linked with raising LOAD risk (odds ratio (OR) = 1.48, 95% confidence interval (CI) = 0.96-2.28, p = 0.07). In subgroup analysis, the phenomenon that men with ALDH2*2 had higher risk for LOAD (OR = 1.72, 95%CI = 1.10-2.67, p = 0.02) was observed. Conclusions: This study comprehends only five existing case-control studies and the result is negative. The positive trend might appear when the sample size is enlarged. In the future, more large-scale casecontrol or cohort studies should be done to enhance the association between ALDH2 polymorphism and AD or other neurodegenerative diseases.