Meta-analyses of genome-wide association studies (GWAS) have identified >240 loci associated with type 2 diabetes (T2D), however most loci have been identified in analyses of European-ancestry individuals. To examine T2D risk in East Asian individuals, we meta-analyzed GWAS data in 77,418 cases and 356,122 controls. In the main analysis, we identified 298 distinct association signals at 178 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 56 loci newly implicated in T2D predisposition. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. New associations include signals in/near GDAP1 , PTF1A , SIX3 , ALDH2 , a microRNA cluster, and genes that affect muscle and adipose differentiation. At another locus, eQTLs at two overlapping T2D signals act through two genes, NKX6-3 and ANK1 , in different tissues. Association studies in diverse populations identify additional loci and elucidate disease genes, biology, and pathways.

https://www.biorxiv.org/content/biorxiv/early/2019/06/28/685172.full.pdf

Identification of type 2 diabetes loci in 433,540 East Asian individuals

Acetaldehyde dehydrogenase 2 (ALDH2) is the key enzyme responsible for metabolism of the alcohol metabolite acetaldehyde in the liver. In addition to conversion of the acetaldehyde molecule, ALDH is also involved in other cellular functions. Recently, many studies have investigated the involvement of ALDH expression in viral hepatitis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), liver fibrosis, and liver cancer. Notably, ALDH2 expression has been linked with liver cancer risk, as well as pathogenesis and prognosis, and has emerged as a promising therapeutic target. Of note, approximately 8% of the world's population, and approximately 30-40% of the population in East Asia carry an inactive ALDH2 gene. This review summarizes new progress in understanding tissue-specific acetaldehyde metabolism by ALDH2 as well as the association of ALDH2 gene polymorphisms with liver disease and cancer. New research directions emerging in the field are also briefly discussed.

/pdf/aldehyde-dehydrogenase-liver-disease-and-cancer-5f5w8cpzkb.pdf

Aldehyde Dehydrogenase, Liver Disease and Cancer.

The role of aldehyde dehydrogenase 2 in cardiovascular disease

Appropriate interventions might improve the prevention of essential hypertension. This requires a comprehensive view of modifiable lifestyle factors (MLFs) distribution and effect. To determine how six MLFs (general adiposity, abdominal adiposity, alcohol consumption, smoking, diet, physical inactivity) for risk of hypertension are distributed and how their combinations affect the risk, a prospective study cohort of 11,923 healthy participants from the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam Study was used. Of these, 1,635 developed hypertension during a mean follow-up of 10.3 years. Mutually exclusive combinations, clustering and interactions of MLFs were then investigated stratifying by sex, Hazard Ratios (HRs) and Population Attributable Risks (PARs%) were calculated. General adiposity alone was sufficient to increase the risk of hypertension (HR = 1.86, PAR% 3.36), and in this cohort it played a major role in enhancing the risk of hypertension, together with smoking and physical inactivity. MLFs had a different impact and a different modulation of risk in women and men, and they showed a remarkable tendency to occur in specific patterns with higher prevalence than expected. This indication can help to promote a holistic approach through multifactorial preventive strategies addressing more than a factor at a time. For prevention of hypertension addressing adiposity together with smoking, promoting at the same time physical activity should be the first choice.

/pdf/traditional-risk-factors-for-essential-hypertension-analysis-3bnmivfud5.pdf

Traditional risk factors for essential hypertension: analysis of their specific combinations in the EPIC-Potsdam cohort.

There is scientific evidence of the positive effect of polyphenols from plant foods on inflammation and oxidative status. The aim of the present study was to investigate whether treatment with a high-polyphenolic nutraceutical reduces the plasmatic concentration of certain oxidative and inflammatory biomarkers in a healthy population. One hundred and eight subjects were selected and stratified by sex in the intervention group (n = 53) and the placebo group (n = 55). Ninety-two subjects completed the study after two 16-week treatment periods separated by a four-week washout period. The results revealed statistically significant differences in subjects treated with the polyphenolic extract compared to the placebo: A decrease in homocysteine, oxidized low-density lipoprotein (OxLDL), TNF-α, sTNFR1, and C-reactive protein (CRP). The most significant decrease was observed for OxLDL (from 78.98 ± 24.48 to 69.52 ± 15.64; p < 0.05) and CRP (from 1.50 ± 0.33 to 1.39 ± 0.37; p < 0.05), both showing significant differences compared to the placebo (p < 0.001). Moreover, catecholamines increased after the administration of the product under investigation, especially in the case of dopamine (from 15.43 ± 2.66 to 19.61 ± 5.73; p < 0.05). Therefore, the consumption of a nutraceutical based on fruit and vegetables with a high polyphenol content seems to improve the parameters related to health benefits (oxidative and inflammatory biomarkers), including remarkable changes in the expression of catecholamines.

Effects of a Fruit and Vegetable-Based Nutraceutical on Biomarkers of Inflammation and Oxidative Status in the Plasma of a Healthy Population: A Placebo-Controlled, Double-Blind, and Randomized Clinical Trial

SCOPE It has been demonstrated that a mutation of MTHFR C677T increases plasma total homocysteine (Hcy) concentration and decreases folate. Natural foods can improve Hcy levels, but the effect of certain foods remains undetermined. The aim of this study was to investigate the association between food groups and Hcy, and to explore the correlations between Hcy and dietary folate/vitamin (Vit) B12 for genotype-specific population. METHODS AND RESULTS A total of 4507 adults were enrolled in this study, all of whom underwent physical examinations and genotyping. A dietary recall questionnaire, which assessed the frequency (F) and quantity (Q) of food consumption, was completed by all. For the male CC group, after adjustment for age and BMI, fish (F) was negatively correlated with Hcy; for the male CT group, fish (F) and eggs (F) were negatively associated with Hcy, whereas cereal/wheat (Q) were positively correlated with Hcy; for the male TT group, fish (F), meat (Q), milk (F), and fruits/vegetables (Q) were negatively associated with Hcy, whereas sugar (Q) and salt (Q) were positively associated with Hcy. For the female CC group, fruits/vegetables (Q), eggs (F) and meat (F) were negatively correlated with Hcy, but soy (F) was positively correlated with Hcy; for the female CT group, eggs (F) and meat (Q) were negatively correlated with Hcy, whereas soy (F), fried foods (F) and salt (Q) were positively correlated with Hcy; for the female TT group, fish(F), eggs (F), and fruits/vegetables (F) were negatively associated with Hcy. Furthermore, we found that Hcy was more closely correlated with folate than with Vit B12 for males (CC, CT and TT) and female TT genotype. However, the correlation between Hcy and Vit B12 was stronger for the female CT/CC groups. CONCLUSION Hcy levels were influenced by food groups to varying degrees, which were based on gender and MTHFR C677T genotypes. Hcy levels were more closely correlated with folate for males (CC, CT and TT) and the female TT group, but it was more closely correlated with Vit B12 for the female CT/CC groups.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/mnfr.201600351

Influence of food groups on plasma total homocysteine for specific MTHFR C677T genotypes in Chinese population.

Hypertension is a multiple factor disease which was influenced by gene, environment, and lifestyle. Several studies confirmed that the ALDH2 rs671 polymorphism is associated with hypertension. However, the evidence remains inconclusive. Whether lifestyle affects blood pressure in different genotype groups have not been clarified, either. The subjects were adult Chinese Han people who received health examination in the period from December 2014 to December 2015. Detection of the ALDH2 r671 polymorphism was determined by polymerase chain reaction. Lifestyle data were collected using self-administered questionnaires. Basic characteristics and fasting venous blood sample were collected at baseline. 4018 subjects were eligible for participation.The frequencies of the ALDH2 rs671 genotype were 68.67% (GG), 28.67%(GL), 2.66%(LL), respectively. Pepole who harbored the L allele were less likely to develop incident hypertension. There was a significant association between food frequency and hypertension in the L genotype group. Fried food intake was significantly increased the risk of hypertension in the L genotype group. Our study suggested that ALDH2 rs671 L-genotypes are protective factors for hypertension in Han Chinese. Consumption of fried food accelerated the development of hypertension in individuals with poor metabolism of acetaldehyde.

/pdf/associations-between-aldehyde-dehydrogenase-2-aldh2-rs671-2s1q2w3a13.pdf

Associations between aldehyde dehydrogenase 2 (ALDH2) rs671 genetic polymorphisms, lifestyles and hypertension risk in Chinese Han people.

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Influence of food groups on plasma total homocysteine for specific MTHFR C677T genotypes in Chinese population.

Associations between aldehyde dehydrogenase 2 (ALDH2) rs671 genetic polymorphisms, lifestyles and hypertension risk in Chinese Han people.