Korean J Leg Med.  2019 May;43(2):71-80. 10.7580/kjlm.2019.43.2.71.

Single Nucleotide Polymorphisms Associated with Alcohol-Induced Flushing Syndrome in Korean Population

• Lee JH
• Seo HJ
• Cho S
• Kim MY
• Lee SD

• KMID: 2448942
• DOI: http://doi.org/10.7580/kjlm.2019.43.2.71

Abstract

Alcohol-induced flushing syndrome is one of the alcohol hypersensitivity reactions commonly found among Asian population. This study was designed to find markers that can predict this particular propensity among Korean population and to assess the applicability of this finding to build a prediction model as forensic DNA phenotyping tool to operate in practical forensic cases. Five hundred seventy unrelated Koreans were genotyped using microfluidic technology with 24 possible candidate single nucleotide polymorphism (SNP) markers. Of the 24 candidate SNPs, four markers, rs671, rs2074356, rs4646776, and rs10849915, on chromosome 12 showed statistically significant association with P-values ranging from 1.39×10⁻¹â´ to 0.004988 among our subjects. All four markers show relatively high specificity values, ranging from 0.804651 to 0.972093, presenting their capabilities as differential SNPs that can distinguish a person with or without alcohol-induced flushing syndrome. Maneuvering these candidate SNPs as well as finding additional potential markers through future studies will help building an appropriate prediction model for Koreans that can be used as supplementary tool for individual identification.

Keyword

Alcohols; Flushing; Aldehyde dehydrogenase; Single nucleotide polymorphism; Koreans

MeSH Terms

Alcohols
Aldehyde Dehydrogenase
Asian Continental Ancestry Group
Chromosomes, Human, Pair 12
DNA
Flushing*
Humans
Hypersensitivity
Microfluidics
Polymorphism, Single Nucleotide*
Sensitivity and Specificity
Alcohols
Aldehyde Dehydrogenase
DNA

Reference

1. Wall TL, Peterson CM, Peterson KP, et al. Alcohol metabolism in Asian-American men with genetic polymorphisms of aldehyde dehydrogenase. Ann Intern Med. 1997; 127:376–379.

2. Baik I, Cho NH, Kim SH, et al. Genome-wide association studies identify genetic loci related to alcohol consumption in Korean men. Am J Clin Nutr. 2011; 93:809–816.

3. Kim J, Oh B, Lim JE, et al. No interaction with alcohol consumption, but independent effect of C12orf51 (HECTD4) on type 2 diabetes mellitus in Korean adults aged 40-69 years: the KoGES_Ansan and Ansung Study. PLoS One. 2016; 11:e0149321.

4. Eriksson CJ, Fukunaga T, Sarkola T, et al. Functional relevance of human adh polymorphism. Alcohol Clin Exp Res. 2001; 25:5 Suppl ISBRA. 157S–163S.

5. Sherva R, Rice JP, Neuman RJ, et al. Associations and interactions between SNPs in the alcohol metabolizing genes and alcoholism phenotypes in European Americans. Alcohol Clin Exp Res. 2009; 33:848–857.

6. Mizoi Y, Ijiri I, Tatsuno Y, et al. Relationship between facial flushing and blood acetaldehyde levels after alcohol intake. Pharmacol Biochem Behav. 1979; 10:303–311.

7. Chen CC, Lu RB, Chen YC, et al. Interaction between the functional polymorphisms of the alcohol-metabolism genes in protection against alcoholism. Am J Hum Genet. 1999; 65:795–807.

8. Crabb DW, Edenberg HJ, Bosron WF, et al. Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity: the inactive ALDH2(2) allele is dominant. J Clin Invest. 1989; 83:314–316.

9. Crabb DW, Matsumoto M, Chang D, et al. Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology. Proc Nutr Soc. 2004; 63:49–63.

10. Linneberg A, Gonzalez-Quintela A, Vidal C, et al. Genetic determinants of both ethanol and acetaldehyde metabolism influence alcohol hypersensitivity and drinking behaviour among Scandinavians. Clin Exp Allergy. 2010; 40:123–130.

11. Peng GS, Yin JH, Wang MF, et al. Alcohol sensitivity in Taiwanese men with different alcohol and aldehyde dehydrogenase genotypes. J Formos Med Assoc. 2002; 101:769–774.

12. Agarwal DP, Harada S, Goedde HW. Racial differences in biological sensitivity to ethanol: the role of alcohol dehydrogenase and aldehyde dehydrogenase isozymes. Alcohol Clin Exp Res. 1981; 5:12–16.

13. Choi IG, Son HG, Yang BH, et al. Scanning of genetic effects of alcohol metabolism gene (ADH1B and ADH1C) polymorphisms on the risk of alcoholism. Hum Mutat. 2005; 26:224–234.

14. Birley AJ, James MR, Dickson PA, et al. Association of the gastric alcohol dehydrogenase gene ADH7 with variation in alcohol metabolism. Hum Mol Genet. 2008; 17:179–189.

15. Matsuo K, Hiraki A, Hirose K, et al. Impact of the alcohol-dehydrogenase (ADH) 1C and ADH1B polymorphisms on drinking behavior in nonalcoholic Japanese. Hum Mutat. 2007; 28:506–510.

16. Shibuya A, Yasunami M, Yoshida A. Genotype of alcohol dehydrogenase and aldehyde dehydrogenase loci in Japanese alcohol flushers and nonflushers. Hum Genet. 1989; 82:14–16.

17. Purcell S, Neale B, Todd-Brown K, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007; 81:559–575.

18. Barrett JC, Fry B, Maller J, et al. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005; 21:263–265.

19. Yang X, Lu X, Wang L, et al. Common variants at 12q24 are associated with drinking behavior in Han Chinese. Am J Clin Nutr. 2013; 97:545–551.

20. Quillen EE, Chen XD, Almasy L, et al. 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. Am J Med Genet B Neuropsychiatr Genet. 2014; 165B:103–110.

21. Zeiner AR, Paredes A, Christensen HD. The role of acetaldehyde in mediating reactivity to an acute dose of ethanol among different racial groups. Alcohol Clin Exp Res. 1979; 3:11–18.

22. Takao A, Shimoda T, Kohno S, et al. Correlation between alcohol-induced asthma and acetaldehyde dehydrogenase-2 genotype. J Allergy Clin Immunol. 1998; 101:576–580.

23. Wolff PH. Ethnic differences in alcohol sensitivity. Science. 1972; 175:449–450.

24. Reed TE, Kalant H, Gibbins RJ, et al. Alcohol and acetaldehyde metabolism in Caucasians, Chinese and Amerinds. Can Med Assoc J. 1976; 115:851–855.

25. Harada S, Agarwal DP, Goedde HW. Aldehyde dehydrogenase deficiency as cause of facial flushing reaction to alcohol in Japanese. Lancet. 1981; 2:982.

26. Yoshida A, Huang IY, Ikawa M. Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in Orientals. Proc Natl Acad Sci U S A. 1984; 81:258–261.

27. Edenberg HJ. The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variants. Alcohol Res Health. 2007; 30:5–13.

28. Kayser M, Schneider PM. DNA-based prediction of human externally visible characteristics in forensics: motivations, scientific challenges, and ethical considerations. Forensic Sci Int Genet. 2009; 3:154–161.

29. Lee JH, Lee HW, Jung KW, et al. Genetic testing for additional evidence during investigations: focus in ethics. Korean J Leg Med. 2015; 39:93–98.