Common variants at 12q24 are associated with drinking behavior in Han Chinese

Yang, Xueli; Lu, Xiangfeng; Wang, Laiyuan; Chen, Shufeng; Li, Jianxin; Cao, Jie; Chen, Jichun; Hao, Yongchen; Liu, Ying; Zhao, Liancheng; Li, Hongfan; Liu, Donghua; Wang, Ligui; Lu, Fanghong; Shen, Chong; Yu, Lin; Wu, Xianping; Zhao, Qi; Xu, Jun‐Fa; Guo, Dongshuang; Peng, Xiaozhong; Huang, Jianfeng; Gu, Dongfeng

doi:10.3945/ajcn.112.046482

Cited by 43 publications

(32 citation statements)

References 22 publications

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“…A genome-wide association study ( GWAS ) of Japanese people found ALDH2 had the strongest association with drinking behavior (27). A similar association was also found in the Han Chinese population, with the association clustered around the ALDH2 gene location on chromosome 12q24 (28). …”

Section: Impact On Human Healthsupporting

confidence: 76%

A Personalized Medicine Approach for Asian Americans with the Aldehyde Dehydrogenase 2*2 Variant

Gross

Zambelli²,

Small³

et al. 2015

Annu. Rev. Pharmacol. Toxicol.

117

122

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Asian Americans are one of the fastest-growing populations in the United States. A relatively large subset of this population carries a unique loss-of-function point mutation in aldehyde dehydrogenase 2 (ALDH2), ALDH2*2. Found in approximately 560 million people of East Asian descent, ALDH2*2 reduces enzymatic activity by approximately 60% to 80% in heterozygotes. Furthermore, this variant is associated with a higher risk for several diseases affecting many organ systems, including a particularly high incidence relative to the general population of esophageal cancer, myocardial infarction, and osteoporosis. In this review, we discuss the pathophysiology associated with the ALDH2*2 variant, describe why this variant needs to be considered when selecting drug treatments, and suggest a personalized medicine approach for Asian American carriers of this variant. We also discuss future clinical and translational perspectives regarding ALDH2*2 research.

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Section: Impact On Human Healthsupporting

confidence: 76%

A Personalized Medicine Approach for Asian Americans with the Aldehyde Dehydrogenase 2*2 Variant

Gross

Zambelli²,

Small³

et al. 2015

Annu. Rev. Pharmacol. Toxicol.

117

122

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“…A significant difference was noticed between our study and the study made by Ji et al That research shows that 37.4% of men and 11.6% of women were occasional binge drinkers, and just 2.9% of the young Chinese people (4.9% of men and 1.3% of women) were usual binge drinkers in 2012 [21], these results reflect, that the Chinese people's alcohol metabolizing enzymes are different [22][23][24]. The preloading is a common habit in many countries and every nation is participating at this event in different proportions.…”

Section: Discussioncontrasting

confidence: 66%

“…There is some difference compared to the data collected by Shah et al in 2009 among medical students, 14% of them do not consume alcohol [20]. Same difference (19.2%) was found in the epidemiology study among Chinese College Students in 2012 [21], but the Chinese people's alcohol-metabolizing enzymes have different genotype, they metabolize alcohol in a different pattern than other populations, so perhaps this is the cause why they consume less alcohol than other people [22][23][24].…”

Section: Discussioncontrasting

confidence: 41%

Romanian young people’s drinking habits

Bucur¹,

Fülöp

Croitoru

2014

Acta Medica Marisiensis

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Objective: Alcohol use can cause social problems. Beside alcoholism the "binge drinking" and the "pre-drinking" could be a harmful form of alcohol use based on scientific literature data. In this study the alcohol use behaviors and associated problems were evaluated among young people aged between 14-30 years. Methods: The study was carried out using a self reporting questionnaire, containing the Alcohol Use Disorders Identification Test (AUDIT) developed by World Health Organization and 10 more questions. This questionnaire was created in two languages (Romanian, Hungarian) and uploaded to the on-line survey page (www.kwiksurveys.com). The link was shared at different Facebook groups. Results: The questionnaire was completed by 933 young people. There was a predominance of females (66.99%) and the participant's average age was 22.12 years (±2.78). The results show that males' relative risk (RR) for alcoholism is 7.18 (CI95%, 3.47-14.85). Majority (539; 57.77%) of the participants had at least one time binge drinking, from this 36.66% were occasionally binge drinkers and 21.11% were regular binge drinkers. More males binge drinkers were found then females (RR: 1.72; CI95%, 1.55-1.90). The people who participate in pre-drinking have RR of 2.14 (CI95%, 1.89-2.41) for binge drinking. The binge drinkers have RR of 2.58 (CI95%, 1.78-3.37) for drunk driving. Conclusions: Binge drinking is a really common habit among young people. Measures to reduce the risk or prevent the harmful consequences of this habit should be employed.

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“…SNPs related to AD, maximum or average alcohol consumption, and/or frequency of consumption were selected through the NHGRI Catalog of Published Genome-Wide Association Studies (Hindorff et al 2009) and considered for AD, maximum drinks, and flushing response in the present sample of males. Two previous case-control GWAS of alcohol consumption (“drinkers” vs. “non-drinkers”) have been performed in Chinese or Japanese populations, each identifying an additional SNP associated with drinking behavior within 1MB of ALDH2 - rs10774610 in CCDC63 (Takeuchi et al 2011) and rs11066280 near C12orf51 (Yang et al 2013). In both papers, the authors note a lack of independence between these SNPs and rs671.…”

Section: Resultsmentioning

confidence: 99%

ALDH2 is associated to alcohol dependence and is the major genetic determinant of “daily maximum drinks” in a GWAS study of an isolated rural chinese sample

Quillen

Chen

Almasy

et al. 2013

American J of Med Genetics Pt B

112

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Alcohol dependence (AD) is a moderately heritable phenotype with a small number of known risk genes mapped via linkage or candidate gene studies. We considered 313 males from among 600 members of documented, extended pedigrees in which AD segregates collected in Northern Hunan Province, China. A joint analysis of both males and females could not be performed as the difference in alcohol consumption variance was too large. Genome-wide association analyses were performed for approximately 300,000 single nucleotide polymorphisms (SNPs). Significant associations found in the ALDH2 region for AD (minimum p = 4.73×10-8) and two AD-related phenotypes: flushing response (minimum p = 4.75×10-26) and maximum drinks in a 24-hour period (minimum p = 1.54×10-16). Association of previous candidate SNP, rs10774610 in CCDC63, was confirmed but resulted from linkage disequilibrium with ALDH2. ALDH2 is strongly associated with flushing response, AD, and maximum drinks in males, with nonsynonymous SNP rs671 explaining 29.2%, 7.9% and 22.9% of phenotypic variation, respectively, in this sample. When rs671 was considered as a candidate SNP in females, it explained 23.6% of the variation in flushing response, but alcohol consumption rates were too low among females – despite familial enrichment for AD – for an adequate test of association for either AD or maximum drinks. These results support a mediating effect of aldehyde dehydrogenase deficiency on alcohol consumption in males and a secondary, culturally-mediated limitation on alcohol consumption by females that should be appropriately modeled in future studies of alcohol consumption in populations where this may be a factor.

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Common variants at 12q24 are associated with drinking behavior in Han Chinese

Cited by 43 publications

References 22 publications

A Personalized Medicine Approach for Asian Americans with the Aldehyde Dehydrogenase 2*2 Variant

A Personalized Medicine Approach for Asian Americans with the Aldehyde Dehydrogenase 2*2 Variant

Romanian young people’s drinking habits

ALDH2 is associated to alcohol dependence and is the major genetic determinant of “daily maximum drinks” in a GWAS study of an isolated rural chinese sample

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