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Differences in individual eating habits may be influenced by genetic factors, in addition to cultural, social or environmental factors. Previous studies suggested that genetic variants within sweet taste receptor genes family were associated with sweet taste perception and the intake of sweet foods. The aim of this study was to conduct a genome-wide association study (GWAS) to find genetic variations that affect confection consumption in a Japanese population. We analysed GWAS data on confection consumption using 14 073 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a semi-quantitative FFQ to estimate food intake that was validated previously. Association of the imputed variants with confection consumption was performed by linear regression analysis with adjustments for age, sex, total energy intake and principal component analysis components 1–3. Furthermore, the analysis was repeated adjusting for alcohol intake (g/d) in addition to the above-described variables. We found 418 SNP located in 12q24 that were associated with confection consumption. SNP with the ten lowest P-values were located on nine genes including at the BRAP, ACAD10 and aldehyde dehydrogenase 2 regions on 12q24.12-13. After adjustment for alcohol intake, no variant was associated with confections intake with genome-wide significance. In conclusion, we found a significant number of SNP located on 12q24 genes that were associated with confections intake before adjustment for alcohol intake. However, all of them lost statistical significance after adjustment for alcohol intake.

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 (ALDH2) has both dehydrogenase and esterase activity; its dehydrogenase activity is closely related to the metabolism of aldehydes produced under oxidative stress (OS). In this review, we recapitulate the enzyme activity of ALDH2 in combination with its protein structure, summarize and show the main mechanisms of ALDH2 participating in metabolism of aldehydes in vivo as comprehensively as possible; we also integrate the key regulatory mechanisms of ALDH2 participating in a variety of physiological and pathological processes related to OS, including tissue and organ fibrosis, apoptosis, aging, and nerve injury-related diseases. On this basis, the regulatory effects and application prospects of activators, inhibitors, and protein post-translational modifications (PTMs, such as phosphorylation, acetylation, S-nitrosylation, nitration, ubiquitination, and glycosylation) on ALDH2 are discussed and prospected. Herein, we aimed to lay a foundation for further research into the mechanism of ALDH2 in oxidative stress-related disease and provide a basis for better use of the ALDH2 function in research and the clinic.

Background： Aldehyde dehydrogenase 2 （ALDH2） is involved in the pathophysiological processes of cardiovascular diseases. Recent studies showed that mutant ALDH2 could increase oxidative stress and is a susceptible factor for hypertension. In addition, wild-type ALDH2 could improve the endothelial functions, therefore reducing the risk of developing atherosclerosis. The aim of the present study was to explore the frequency of the Glu504Lys polymorphism of the ALDH2 gene and its relation to carotid intima-media thickness （CIMT） in a group of patients with essential hypertension （EH） and to investigate the association between the Glu504Lys polymorphism and CIMT in Chinese Han patients with EH. Methods： In this study, 410 Chinese Han patients with EH who received physical examinations at the People＇s Hospital of Sichuan Province （China） were selected. DNA microarray chip was used for the genotyping of the Glu504Lys polymorphism of the ALDH2 gene. The differences in CIMT among patients with different Glu504Lys ALDH2 genotypes were analyzed. Results： The mean CIMT of the patients carrying AA/AG and GG genotypes was 1.02 ± 0.31 mm and 0.78 ±0.28 mm, respectively. One-way ANOVA showed that the CIMT of the patients carrying the AA/AG genotype was significantly higher than in the ones carrying the GG genotype （P 〈 0.001）. Multivariate logistic regression showed that the Glu504Lys AA/AG genotype of the ALDH2 gene was one of the major factors influencing the CIMT in patients with EH （odds ratio = 3.73 l, 95% confidence interval = 1.589-8.124, P = 0.001）. Conclusions： The Glu504Lys polymorphism of the ALDH2 gene is associated with the CIMT of Chinese Han patients with EH in Sichuan, China.

Aldehyde dehydrogenase 2（ALDH2）is an important factor in inhibiting oxidative stress and has been shown to protect against renal ischemia/reperfusion injury.Therefore,we hypothesized that ALDH_2 could reduce spinal cord ischemia/reperfusion injury.Spinal cord ischemia/reperfusion injury was induced in rats using the modified Zivin＇s method of clamping the abdominal aorta.After successful model establishment,the agonist group was administered a daily consumption of 2.5%alcohol.At 7 days post-surgery,the Basso,Beattie,and Bresnahan score significantly increased in the agonist group compared with the spinal cord ischemia/reperfusion injury group.ALDH_2expression also significantly increased and the number of apoptotic cells significantly decreased in the agonist group than in the spinal cord ischemia/reperfusion injury group.Correlation analysis revealed that ALDH_2 expression negatively correlated with the percentage of TUNEL-positive cells（r=-0.485,P〈0.01）.In summary,increased ALDH_2 expression protected the rat spinal cord against ischemia/reperfusion injury by inhibiting apoptosis.

Background：Nitroglycerin （NTG） is one of the few immediate treatments for acute angina.Aldehyde dehydrogenase 2 （ALDH2） is a key enzyme in the human body that facilitates the biological metabolism of NTG.The biological mechanism of NTG serves an important function in NTG efficacy.Some reports still contradict the results that the correlation between ALDH2 gene polymorphisms and NTG and its clinical efficacy is different.However,data on NTG measurement by pain relief are subjective.This study aimed to investigate the influence ofALDH2 gene polymorphism on intervention with sublingual NTG using noninvasive hemodynamic parameters of cardiac output （CO） and systemic vascular resistance （SVR） in Northern Chinese Han population.Methods：This study selected 559 patients from the Affiliated Hospital of Qingdao University.A total of 203 patients presented with coronary heart disease （CHD） and 356 had non-CHD （NCHD） cases.All patient ALDH2 genotypes （G504A） were detected and divided into two types：Wild （GG） and mutant （GA/AA）.Among the CHD group,103 were wild-type cases,and 100 were mutant-type cases.Moreover,196 cases were wild-type,and 160 cases were mutant type among the NCHD volunteers.A noninvasive hemodynamic detector was used to monitor the CO and the SVR at the 0,5,and 15 minute time points after medication with 0.5 mg sublingual NTG.Two CO and SVR indicators were used for a comparative analysis of all case genotypes.Results：Both CO and SVR indicators significantly differed between the wild and mutant genotypes at various time points after intervention with sublingual NTG at 5 and 15 minutes in the NCHD （F =16.460,15.003,P =0.000,0.000） and CHD groups （F =194.482,60.582,P =0.000,0.000）.All CO values in the wild-type case of both NCHD and CHD groups increased,whereas those in the mutant type decreased.The CO and △CO differences were statistically significant （P 〈 0.05; P 〈 0.05）.The SVR and △SVR changed between the wild-and mutant-type cases at all-time points in both NCHD and CHD groups had statistically significant differences （P 〈 0.05; P 〈 0.05）.Conclusion：ALDH2 （G504A） gene polymorphism is associated with changes in noninvasive hemodynamic parameters （i.e.CO and SVR） after intervention with sublingual NTG.This gene polymorphism may influence the effect of NTG intervention on Northern Chinese Han population.

Chronic stress is strongly associated with the occurrence and development of depression and cardiovascular disease. Stress can induce altered mitochondrial function and activation of apoptosis in the cardio-cerebral system. However, it is unknown whether the protein kinase C ε (PKCε)-aldehyde dehydrogenase 2 (ALDH2) pathway is altered under chronic stress, and this study sought to address this question. A rat model of depression was established using a chronic unpredictable mild stress (CUMS) protocol. After experiencing CUMS for 4 weeks, the sucrose preference test and the forced swim test verified depressive-like behaviors. Enzyme linked immunosorbent assays showed that ALDH2 activity was decreased in the rat hippocampus and prefrontal cortex, but was not altered in the myocardium. Western blot assays demonstrated reduced levels of ALDH2 and PKCε, but increased levels of 4-hydroxy-2-nonenal (4HNE) adducts. Caspase-3 expression did not obviously alter, but active forms of caspase-3 were increased in the hippocampus and prefrontal cortex. In the myocardium, expression of ALDH2, PKCε and 4HNE adducts did not remarkably alter; while caspase-3 expression was reduced and the active forms of caspase-3 were upregulated. Pearson's correlation test demonstrated that expression of 4HNE adducts was positively correlated with levels of the active forms of caspase-3 in the hippocampus and prefrontal cortex, but not in the myocardium. In conclusion, chronic stress can damage the PKCε-ALDH2 signaling pathway in the hippocampus and prefrontal cortex, but not in the myocardium. Moreover, 4HNE is associated with active forms of caspase-3 in the hippocampus and prefrontal cortex.

Folate consumption is inversely associated with the risk of oral and pharyngeal cancer (OPC) and potentially interacts with alcohol drinking in the risk of OPC. Aldehyde dehydrogenase 2 (ALDH2) gene polymorphism is known to interact with alcohol consumption. The aim of this study was to investigate potential interaction between folate, alcohol drinking, and ALDH2 polymorphism in the risk of OPC in a Japanese population. The study group comprised 409 head and neck cancer cases and 1227 age-matched and sex-matched noncancer controls; of these, 251 cases and 759 controls were evaluated for ALDH rs671 polymorphism. Associations were assessed by odds ratios and 95% confidence intervals in multiple logistic regression models. We observed an inverse association between folate consumption and OPC risk. The odds ratio for high folate intake was 0.53 (95% confidence interval: 0.36–0.77) relative to low intake (P trend = 0.003). This association was consistent across strata of sex, age, smoking, and ALDH2 genotypes. Interaction between folate consumption, drinking, and ALDH2 genotype was remarkable (three-way interaction, P<0.001). We observed significant interaction among folate, drinking, and ALDH2 genotype in the Japanese population.

Heatstroke (HS) can cause acute lung injury (ALI). Heat stress induces inflammation and apoptosis via reactive oxygen species (ROS) and endogenous reactive aldehydes. Endothelial dysfunction also plays a crucial role in HS-induced ALI. Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that detoxifies aldehydes such as 4-hydroxy-2-nonenal (4-HNE) protein adducts. A single point mutation in ALDH2 at E487K (ALDH2*2) intrinsically lowers the activity of ALDH2. Alda-1, an ALDH2 activator, attenuates the formation of 4-HNE protein adducts and ROS in several disease models. We hypothesized that ALDH2 can protect against heat stress-induced vascular inflammation and the accumulation of ROS and toxic aldehydes. Homozygous ALDH2*2 knock-in (KI) mice on a C57BL/6J background and C57BL/6J mice were used for the animal experiments. Human umbilical vein endothelial cells (HUVECs) were used for the in vitro experiment. The mice were directly subjected to whole-body heating (WBH, 42°C) for 1 h at 80% relative humidity. Alda-1 (16 mg/kg) was administered intraperitoneally prior to WBH. The severity of ALI was assessed by analyzing the protein levels and cell counts in the bronchoalveolar lavage fluid, the wet/dry ratio and histology. ALDH2*2 KI mice were susceptible to HS-induced ALI in vivo . Silencing ALDH2 induced 4-HNE and ROS accumulation in HUVECs subjected to heat stress. Alda-1 attenuated the heat stress-induced activation of inflammatory pathways, senescence and apoptosis in HUVECs. The lung homogenates of mice pretreated with Alda-1 exhibited significantly elevated ALDH2 activity and decreased ROS accumulation after WBH. Alda-1 significantly decreased the WBH-induced accumulation of 4-HNE and p65 and p38 activation. Here, we demonstrated the crucial roles of ALDH2 in protecting against heat stress-induced ROS production and vascular inflammation and preserving the viability of ECs. The activation of ALDH2 by Alda-1 attenuates WBH-induced ALI in vivo .

Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that plays an important role in aldehyde detoxification. A large percentage (30–50%) of the East Asian population carry a single point mutation in the ALDH2 gene (ALDH2*2 variant) that causes a severe reduction or lack of ALDH2 enzyme activity, and leads to disrupted cellular homeostasis due to the accumulation of toxic reactive aldehydes. The ALDH2*2 variant has been associated with several degenerative diseases, with evidence suggesting a link to cardiovascular disease, potentially mediated by endothelial dysfunction. This, however, remains to be confirmed. We aimed to investigate whether the ALDH2*2 variant is associated with impaired endothelial function in young, healthy East Asians. Twenty‐two participants were genotyped and divided into non‐carriers (ALDH2*1/*1; n = 12; 7 females and 5 males; age = 23 ± 3 years; height = 167.4 ± 8.7 cm; body mass = 60.1 ± 9.0 kg) and carriers (ALDH2*1/*2 and ALDH2*2/*2; n = 10; 8 females and 2 males; age = 24 ± 5 years; height = 162.6 ± 10.1 cm; body mass = 62.1 ± 9.7 kg) of the ALDH2*2 allele. Endothelial function was assessed via flow‐mediated dilation (FMD) following current guidelines. Carriers displayed lower FMD, either absolute or relative, which was not statistically significant but approached significance (unpaired t‐test) (FMD%: non‐carriers = 10.2 ± 1.9% vs. carriers = 8.1% ± 3.1%, P = 0.079, effect size: Cohen's d = 0.82; FMDabs: non‐carriers = 0.32 ± 0.06 mm vs. carriers = 0.26 ± 0.09 mm, P = 0.082, effect size: Cohen's d = 0.78). In conclusion, our data seem to suggest that the ALDH2*2 variant impairs endothelial function even in young and healthy individuals without the presence of other stressor agents. Future studies with larger sample size are necessary to confirm our findings. What is the central question of this study? Do carriers of the mutation in the ALDH2 gene that results in sustained exposure to increased levels of reactive aldehydes display impaired endothelial function assessed with the flow‐mediated dilation (FMD) technique? What is the main finding and its importance? FMD was lower in young and healthy carriers of the mutated allele when compared to non‐carrier controls. The difference is physiologically relevant, but did not reach statistical significance. The findings are preliminary and suggest that sustained aldehydic load can have detrimental effects on vascular function, even in young and healthy individuals.