Associations between ALDH Genetic Variants, Alcohol Consumption, and the Risk of Nasopharyngeal Carcinoma in an East Asian Population

Nasopharyngeal carcinoma (NPC) and alcohol flush syndrome are thought to be strongly influenced by genetic factors and are highly prevalent amongst East Asians. Diminished activity of aldehyde dehydrogenase (ALDH), a major enzyme in the alcohol-metabolizing pathway, causes the flushing syndrome associated with alcoholic consumption. The genetic effect of ALDH isoforms on NPC is unknown. We therefore investigated the association between the genetic polymorphisms of all 19 ALDH isoforms and NPC among 458 patients with NPC and 1672 age- and gender-matched healthy controls in Taiwan. Single-nucleotide polymorphisms (SNPs) located between the 40,000 base pairs upstream and downstream of the 19 ALDH isoform coding regions were collected from two genome-wise association studies conducted in Taiwan and from the Taiwan Biobank. Thirteen SNPs located on ALDH4A1, ALDH18A1, ALDH3B2, ALDH1L2, ALDH1A2, and ALDH2 Glu487Lys (rs671) were associated with NPC susceptibility. Stratification by alcohol status revealed a cumulative risk effect for NPC amongst drinkers and non-drinkers, with odds ratios of 4.89 (95% confidence interval 2.15–11.08) and 3.57 (1.97–6.47), respectively. A synergistic effect was observed between SNPs and alcohol. This study is the first to report associations between genetic variants in 19 ALDH isoforms, their interaction with alcohol consumption and NPC in an East Asian population.

Association of ABCG2 rs2231142 Allele and BMI With Hyperuricemia in an East Asian Population

Objectives: Genetic variants and obesity are risk factors for hyperuricemia (HUA). Recent genome-wide association studies have identified ABCG2 rs2231142 as one of the most prominent genetic variants for HUA in an East Asian population. Nevertheless, no large-scale studies have demonstrated any interactive effects between this variant and obesity on serum urate level in Asians. This study aimed to determine the interaction of ABCG2 rs2231142 variant and body mass index (BMI) and its effect on risk of HUA in an East Asian population.Methods: The study was conducted using the Taiwan Biobank database, a population-based biomedical research database of patients with Taiwanese Han Chinese ancestry aged 30–70years between September 2014 and May 2017. Detailed physical information on participants were collected by questionnaires and genotyping using Affymetrix TWB 650K SNP chip. The primary outcome was HUA, defined as a serum uric acid level>7.0mg/dl. Odds ratio (OR) of HUA was analyzed using logistic regression models and the effects of interaction between ABCG2 rs2231142 variants and BMI on serum uric acid level were explored.Results: We identified 25,245 subjects, 4,228 (16.75%) of whom had HUA. The prevalence of HUA was 30% in men and 3.8% in women. The risk of HUA was significantly associated with ABCG2 rs2231142 risk T allele, with more HUA in TT genotype (OR: 2.40, 95% CI: 2.11–2.72, p<0.001) and TG genotype (OR: 1.64, 95% CI: 1.51–1.78, p<0.001) in men, and TT genotype (OR: 2.42, 95% CI: 1.83–3.20, p<0.001) and TG genotype (OR: 1.82, 95% CI: 1.46–2.23, p<0.001) in women, compared with their counterparts. Moreover, we found a strong genetic-environmental interaction associated with the risk of HUA. There was increased risk of HUA by the interaction of ABCG2 rs2231142 variant and BMI for TT genotype (OR: 7.42, 95% CI: 2.54–21.7, p<0.001) and TG genotype (OR: 4.25, 95% CI: 2.13–8.47, p<0.001) in men compared with the GG genotype in men, and for TT genotype (OR: 25.43, 95% CI: 3.75–172.41, p<0.001) and TG genotype (OR: 3.05, 95% CI: 0.79–11.71, p=0.011) in women compared with the GG genotype in women.Conclusion: The risk of HUA was markedly increased by the interaction of ABCG2 rs2231142 variant and BMI, both in men and in women. Body weight control and reduction in BMI are recommended in high-risk patients with the ABCG2 rs2231142 risk T allele.

Association between the interferon-γ +874T/A polymorphism and susceptibility to hepatitis B virus infection: a meta-analysis

Objective This study investigated the correlation between the interferon (IFN)-γ +874T/A polymorphism and hepatitis B virus (HBV) susceptibility using meta-analysis. Methods PubMed, EMBASE, Web of Science, CNKI, and China Wanfang databases were searched for case–control studies investigating the IFN-γ +874T/A polymorphism and HBV susceptibility from the time of database establishment to April 2020. Stata 15.0 software was used, and the subgroups of ethnicity and Hardy–Weinberg equilibrium were analyzed. Results Thirteen articles were included in this study. Significant differences were seen in the allelic model, dominant model, homozygous model, and heterozygous model, but heterogeneity was high. Analysis of the East Asian population revealed combined odds ratios of the allelic model (T vs. A), dominant model (TT + TA vs. AA), homozygous model (TT vs. AA), and heterozygous model (TA vs. AA) of 0.61, 0.56, 0.50, and 0.59, respectively. The difference was significant and the heterogeneity low. The recessive model showed no significance in the overall comparison, or in East Asian and Caucasian populations. Conclusions The IFN-γ +874T/A polymorphism is associated with the risk of HBV, especially in the East Asian population. Individuals with the T allele and TT and TA genotypes have a reduced risk of HBV infection.