ADH1B和ALDH2基因多态性与相关疾病研究进展

doi:10.3969/j.issn.1673-8640.2019.03.019

摘要/Abstract

摘要：

乙醇脱氢酶（ADH）和乙醛脱氢酶（ALDH）是人体肝脏内乙醇代谢的关键酶,共同构成ADH氧化体系。ADH1B和ALDH2分别是ADH和ALDH的2个重要亚型。ADH1B和ALDH2基因多态性与多种疾病,如消化系统疾病、神经退行性变及代谢性疾病等相关。文章对ADH1B及ALDH2基因多态性与相关疾病的关系进行综述,以期为疾病的预防和诊断提供新的思路。

关键词: 乙醇脱氢酶1B, 乙醛脱氢酶2, 基因多态性, 疾病

Abstract:

Alcohol dehydrogenase （ADH） and aldehyde dehydrogenase （ALDH）are key enzymes of alcohol metabolism in human liver,which constitute ethanol dehydrogenase oxidation system. ADH1B and ALDH2 are 2 important subtypes of ADH and ALDH,respectively. ADH1B and ALDH2 gene polymorphisms are associated with a variety of diseases,such as digestive system diseases,neurodegenerative disorders and metabolic diseases. In this review,the gene polymorphisms of ADH1B and ALDH2 and their related diseases are reviewed to provide new ideas for the prevention and diagnosis of diseases.

Key words: Alcohol dehydrogenase 1B, Aldehyde dehydrogenase 2, Gene polymorphism, Disease

中图分类号:

Q554

张晓敏, 刘静, 高世超, 杨婷婷, 王培昌. ADH1B和ALDH2基因多态性与相关疾病研究进展[J]. 检验医学, 2019, 34(3): 271-275.

ZHANG Xiaomin, LIU Jing, GAO Shichao, YANG Tingting, WANG Peichang. Research progress of gene polymorphisms of ADH1B and ALDH2 and their related diseases[J]. Laboratory Medicine, 2019, 34(3): 271-275.

图/表 2

参考文献 35

[1]	LEE S L,LEE Y P,WU M L,et al.Inhibition of human alcohol and aldehyde dehydrogenases by aspirin and salicylate: assessment of the effects on first-pass metabolism of ethanol[J]. Biochem Pharmacol,2015,95(1):71-79.
[2]	JIANG S,TONG Y,ZHAO R,et al.An improved PCR-CTPP assay for the detection of ADH1B Arg48His polymorphism[J]. J Clin Lab Anal,2018,32(2):e22268.
[3]	LI R,ZHAO Z,SUN M,et al.ALDH2 gene polymorphism in different types of cancers and its clinical significance[J]. Life Sci,2016,147:59-66.
[4]	孙宇晶,线海鹏,刘向祎,等. 等位基因特异荧光PCR检测ALDH2基因多态性[J]. 检验医学,2017,32(4):267-271.
[5]	ORYWAL K,SZMITKOWSKI M.Alcohol dehydrogenase and aldehyde dehydrogenase in malignant neoplasms[J]. Clin Exp Med, 2017,17(2):131-139.
[6]	DRUESNE-PECOLLO N,TEHARD B,MALLET Y,et al.Alcohol and genetic polymorphisms:effect on risk of alcohol-related cancer[J]. Lancet Oncol,2009,10(2):173-180.
[7]	AHMADI N,CRNIC A,SEELY A J,et al.Impact of surgical approach on perioperative and long-term outcomes following esophagectomy for esophageal cancer[J]. Surg Endosc,2018,32(4):1892-1900.
[8]	KAGEMOTO K,URABE Y,MIWATA T,et al.ADH1B and ALDH2 are associated with metachronous SCC after endoscopic submucosal dissection of esophageal squamous cell carcinoma[J]. Cancer Med, 2016,5(7):1397-1404.
[9]	MATEJCIC M,GUNTER M J,FERRARI P.Alcohol metabolism and oesophageal cancer: a systematic review of the evidence[J]. Carcinogenesis, 2017,38(9):859-872.
[10]	HORIGUCHI N,TAHARA T,YAMADA H.In vivo diagnosis of early-stage gastric cancer found after Helicobacter pylori eradication using probe-based confocal laser endomicroscopy[J]. Dig Endosc,2018,30(2):219-227.
[11]	GHOSH S,BANKURA B,GHOSH S,et al.Polymorphisms in ADH1B and ALDH2 genes associated with the increased risk of gastric cancer in West Bengal, India[J]. BMC Cancer,2017,17(1):782.
[12]	YANG S,LEE J,CHOI I J,et al.Effects of alcohol consumption,ALDH2 rs671 polymorphism,and Helicobacter pylori infection on the gastric cancer risk in a Korean population[J]. Oncotarget,2017,8(4):6630-6641.
[13]	HIDAKA A, SASAZUKI S,MATSUO K,et al.Genetic polymorphisms of ADH1B,ADH1C and ALDH2,alcohol consumption,and the risk of gastric cancer:the Japan Public Health Center-based prospective study[J]. Carcinogenesis,2015,36(2):223-231.
[14]	袁青,薛亚东,郑雅萍,等. 乙醛脱氢酶2基因多态性及生活习惯与胃癌易感性的相关性分析[J]. 检验医学,2016,31(7):584-587.
[15]	CHIANG C P, JAO S W,LEE S P,et al.Expression pattern,ethanol-metabolizing activities,and cellular localization of alcohol and aldehyde dehydrogenases in human large bowel: association of the functional polymorphisms of ADH and ALDH genes with hemorrhoids and colorectal cancer[J]. Alcohol,2012,46(1):37-49.
[16]	CROUS-BOU M,RENNERT G,CUADRAS D,et al.Polymorphisms in alcohol metabolism genes ADH1B and ALDH2,alcohol consumption and colorectal cancer[J].PLoS ONE,2013,8(11):e80158.
[17]	NA H K,LEE J Y. Molecular basis of alcohol-related gastric and colon cancer[J]. Int J Mol Sci,2017,18(6):pii:E1116.
[18]	HAGSTRÖM H,HEMMINGSSON T,DISCACCIATI A,et al. Alcohol consumption in late adolescence is associated with an increased risk of severe liver disease later in life[J]. J Hepatol,2018,68(3):505-510.
[19]	YOKOYAMA A,MIZUKAMI T,MATSUI T,et al.Genetic polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 and liver cirrhosis, chronic calcific pancreatitis, diabetes mellitus, and hypertension among Japanese alcoholic men[J]. Alcohol Clin Exp Res,2013,37(8):1391-1401.
[20]	YOKOYAMA A,TANIKI N,HARA S,et al.Slow-metabolizing ADH1B and inactive heterozygous ALDH2 increase vulnerability to fatty liver in Japanese men with alcohol dependence[J]. J Gastroenterol,2018,53(6):660-669.
[21]	ABE H,AIDA Y,SEKI N,et al.Aldehyde dehydrogenase 2 polymorphism for development to hepatocellular carcinoma in East Asian alcoholic liver cirrhosis[J]. J Gastroenterol Hepatol,2015,30(9):1376-1383.
[22]	MROCZKO B,GROBLEWSKA M,LITMAN-ZAWADZKA A,et al.Amyloid β oligomers (AβOs) in Alzheimer's disease[J]. J Neural Transm (Vienna),2018,125(2):177-191.
[23]	张跃其,张强,王培昌,等. 阿尔茨海默病及帕金森病相关基因突变位点的研究进展[J]. 中华检验医学杂志,2016,39(7):540-543.
[24]	LUSTBADER J W,CIRILLI M,LIN C,et al.ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease[J]. Science,2004,304(5669):448-452.
[25]	BERNTSEN S,KRAGSTRUP J,SIERSMA V,et al.Alcohol consumption and mortality in patients with mild Alzheimer's disease: a prospective cohort study[J]. BMJ Open,2015,5(12):e007851.
[26]	MA L,LU Z N.Role of ADH1B rs1229984 and ALDH2 rs671 gene polymorphisms in the development of Alzheimer's disease[J]. Genet Mol Res,2016,15(4):15048740.
[27]	ZHAO Y,WANG C.Glu504Lys single nucleotide polymorphism of aldehyde dehydrogenase 2 gene and the risk of human diseases[J]. Biomed Res Int,2015,2015:174050.
[28]	SONG J J,OH S M,KWON O C,et al.Cografting astrocytes improves cell therapeutic outcomes in a Parkinson's disease model[J]. J Clin Invest,2018,128(1):463-482.
[29]	CHEN C H,JOSHI A U,MOCHLY-ROSEN D.The role of mitochondrial aldehyde dehydrogenase 2 (ALDH2) in neuropathology and neurodegeneration[J]. Acta Neurol Taiwan,2016,25(4):111-123.
[30]	ZHAO C C,CAI H B,WANG H,et al.Role of ADH2 and ALDH2 gene polymorphisms in the development of Parkinson's disease in a Chinese population[J]. Genet Mol Res,2016,15(3):15038606.
[31]	GOLDSTEIN D S,SULLIVAN P,COONEY A,et al.Rotenone decreases intracellular aldehyde dehydrogenase activity: implications for the pathogenesis of Parkinson's disease[J]. J Neurochem,2015,133(1):14-25.
[32]	GUTTMANN A,KRASNOKUTSKY S,PILLINGER M H,et al.Pegloticase in gout treatment-safety issues,latest evidence and clinical considerations[J]. Ther Adv Drug Saf,2017,8(12):379-388.
[33]	SAKIYAMA M,MATSUO H,AKASHI A,et al.Independent effects of ADH1B and ALDH2 common dysfunctional variants on gout risk[J]. Sci Rep,2017,7(1):2500.
[34]	ZHANG D,YANG M,ZHOU D,et al.The polymorphism rs671 at ALDH2 associated with serum uric acid levels in Chinese Han males: a genome-wide association study[J]. Gene,2018,651:62-69.
[35]	HASHIMOTO M,WATANABE M,UEMATSU Y,et al.Relationships of alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) genotypes with alcohol sensitivity, drinking behavior and problem drinking in Japanese older men[J]. Environ Health Prev Med,2016,21(3):138-148.

基因	SNP位点	基因型	氨基酸变异	相关疾病	发病风险
ADH1B	rs1229984	GG	Arg/Arg	食管鳞癌、阿尔茨海默病	升高
				肝硬化、脂肪肝	升高
		AA、GA	His/His、Arg/His	痛风	升高
	rs17033	AA	His/His	结直肠癌	升高
	rs4147536	GG、GA		胃癌	升高
ALDH2	rs671	TT		胃癌	降低
		GG	Glu/Glu	肝硬化、肝细胞肝癌	升高
		GA	Glu/Lys	食管鳞癌、脂肪肝	升高
		GA、AA	Glu/Lys、Lys/Lys	胃癌	升高
		GA、AA	Glu/Lys、Lys/Lys	阿尔茨海默病、帕金森病、痛风	升高

基因	SNP位点	基因型	氨基酸变异	相关疾病	发病风险
ADH1B	rs1229984	GG	Arg/Arg	食管鳞癌、阿尔茨海默病	升高
				肝硬化、脂肪肝	升高
		AA、GA	His/His、Arg/His	痛风	升高
	rs17033	AA	His/His	结直肠癌	升高
	rs4147536	GG、GA		胃癌	升高
ALDH2	rs671	TT		胃癌	降低
		GG	Glu/Glu	肝硬化、肝细胞肝癌	升高
		GA	Glu/Lys	食管鳞癌、脂肪肝	升高
		GA、AA	Glu/Lys、Lys/Lys	胃癌	升高
		GA、AA	Glu/Lys、Lys/Lys	阿尔茨海默病、帕金森病、痛风	升高