Association Between Aldehyde Dehydrogenase 2 Glu504Lys Polymorphism and Alcoholic Liver Disease

Binxia Chang, Shuli Hao, Longyu Zhang, Miaomiao Gao, Ying Sun, Ang Huang, Guangju Teng, Baosen Li, David Crabb, Praveen Kusumanchi, Li Wang, Suthat Liangpunsakul, Zhengsheng Zou

Research output: Contribution to journalArticle

Abstract

Background: Only a subset of patients with excessive alcohol use develop alcoholic liver disease (ALD), though the exact mechanism is not completely understood. Once ingested, alcohol is metabolized by 2 key oxidative enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). There are 2 major ALDH isoforms, cytosolic and mitochondrial, encoded by the aldehyde ALDH1 and ALDH2 genes, respectively. The ALDH2 gene was hypothesized to alter genetic susceptibility to alcohol dependence and alcohol-induced liver diseases. The aim of this study is to determine the association between aldehyde dehydrogenase 2 (rs671) glu504lys polymorphism and ALD. Methods: ALDH2 genotyping was performed in 535 healthy controls and 281 patients with ALD. Results: The prevalence of the common form of the single nucleotide polymorphism rs671, 504glu (glu/glu) was significantly higher in patients with ALD (95.4%) compared to that of controls (73.7%, P < 0.0001). Among controls, 23.7% had the heterozygous (glu/lys) genotype compared to 4.6% in those with ALD (odds ratio [OR] = 0.16, 95% CI: 0.09-0.28). The allele frequency for 504lys allele in patients with ALD was 2.3%, compared to 14.5% in healthy controls (OR = 0.13, 95% CI: 0.07-0.24). Conclusions: Patients with ALDH2 504lys variant were less associated with ALD compared to those with ALDH2 504glu using both genotypic and allelic analyses.

Original languageEnglish (US)
JournalAmerican Journal of the Medical Sciences
DOIs
StateAccepted/In press - Jan 1 2018

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Alcoholic Liver Diseases
Aldehyde Dehydrogenase
Alcohols
Odds Ratio
Alcohol Dehydrogenase
Genetic Predisposition to Disease
Gene Frequency
Aldehydes
Alcoholism
Genes
Single Nucleotide Polymorphism
Liver Diseases
Protein Isoforms
Alleles
Genotype
Enzymes

Keywords

  • Alcoholic liver disease
  • Aldehyde dehydrogenase
  • Gene polymorphism
  • Risk

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Association Between Aldehyde Dehydrogenase 2 Glu504Lys Polymorphism and Alcoholic Liver Disease. / Chang, Binxia; Hao, Shuli; Zhang, Longyu; Gao, Miaomiao; Sun, Ying; Huang, Ang; Teng, Guangju; Li, Baosen; Crabb, David; Kusumanchi, Praveen; Wang, Li; Liangpunsakul, Suthat; Zou, Zhengsheng.

In: American Journal of the Medical Sciences, 01.01.2018.

Research output: Contribution to journalArticle

Chang, Binxia ; Hao, Shuli ; Zhang, Longyu ; Gao, Miaomiao ; Sun, Ying ; Huang, Ang ; Teng, Guangju ; Li, Baosen ; Crabb, David ; Kusumanchi, Praveen ; Wang, Li ; Liangpunsakul, Suthat ; Zou, Zhengsheng. / Association Between Aldehyde Dehydrogenase 2 Glu504Lys Polymorphism and Alcoholic Liver Disease. In: American Journal of the Medical Sciences. 2018.
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abstract = "Background: Only a subset of patients with excessive alcohol use develop alcoholic liver disease (ALD), though the exact mechanism is not completely understood. Once ingested, alcohol is metabolized by 2 key oxidative enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). There are 2 major ALDH isoforms, cytosolic and mitochondrial, encoded by the aldehyde ALDH1 and ALDH2 genes, respectively. The ALDH2 gene was hypothesized to alter genetic susceptibility to alcohol dependence and alcohol-induced liver diseases. The aim of this study is to determine the association between aldehyde dehydrogenase 2 (rs671) glu504lys polymorphism and ALD. Methods: ALDH2 genotyping was performed in 535 healthy controls and 281 patients with ALD. Results: The prevalence of the common form of the single nucleotide polymorphism rs671, 504glu (glu/glu) was significantly higher in patients with ALD (95.4{\%}) compared to that of controls (73.7{\%}, P < 0.0001). Among controls, 23.7{\%} had the heterozygous (glu/lys) genotype compared to 4.6{\%} in those with ALD (odds ratio [OR] = 0.16, 95{\%} CI: 0.09-0.28). The allele frequency for 504lys allele in patients with ALD was 2.3{\%}, compared to 14.5{\%} in healthy controls (OR = 0.13, 95{\%} CI: 0.07-0.24). Conclusions: Patients with ALDH2 504lys variant were less associated with ALD compared to those with ALDH2 504glu using both genotypic and allelic analyses.",
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author = "Binxia Chang and Shuli Hao and Longyu Zhang and Miaomiao Gao and Ying Sun and Ang Huang and Guangju Teng and Baosen Li and David Crabb and Praveen Kusumanchi and Li Wang and Suthat Liangpunsakul and Zhengsheng Zou",
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T1 - Association Between Aldehyde Dehydrogenase 2 Glu504Lys Polymorphism and Alcoholic Liver Disease

AU - Chang, Binxia

AU - Hao, Shuli

AU - Zhang, Longyu

AU - Gao, Miaomiao

AU - Sun, Ying

AU - Huang, Ang

AU - Teng, Guangju

AU - Li, Baosen

AU - Crabb, David

AU - Kusumanchi, Praveen

AU - Wang, Li

AU - Liangpunsakul, Suthat

AU - Zou, Zhengsheng

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Only a subset of patients with excessive alcohol use develop alcoholic liver disease (ALD), though the exact mechanism is not completely understood. Once ingested, alcohol is metabolized by 2 key oxidative enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). There are 2 major ALDH isoforms, cytosolic and mitochondrial, encoded by the aldehyde ALDH1 and ALDH2 genes, respectively. The ALDH2 gene was hypothesized to alter genetic susceptibility to alcohol dependence and alcohol-induced liver diseases. The aim of this study is to determine the association between aldehyde dehydrogenase 2 (rs671) glu504lys polymorphism and ALD. Methods: ALDH2 genotyping was performed in 535 healthy controls and 281 patients with ALD. Results: The prevalence of the common form of the single nucleotide polymorphism rs671, 504glu (glu/glu) was significantly higher in patients with ALD (95.4%) compared to that of controls (73.7%, P < 0.0001). Among controls, 23.7% had the heterozygous (glu/lys) genotype compared to 4.6% in those with ALD (odds ratio [OR] = 0.16, 95% CI: 0.09-0.28). The allele frequency for 504lys allele in patients with ALD was 2.3%, compared to 14.5% in healthy controls (OR = 0.13, 95% CI: 0.07-0.24). Conclusions: Patients with ALDH2 504lys variant were less associated with ALD compared to those with ALDH2 504glu using both genotypic and allelic analyses.

AB - Background: Only a subset of patients with excessive alcohol use develop alcoholic liver disease (ALD), though the exact mechanism is not completely understood. Once ingested, alcohol is metabolized by 2 key oxidative enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). There are 2 major ALDH isoforms, cytosolic and mitochondrial, encoded by the aldehyde ALDH1 and ALDH2 genes, respectively. The ALDH2 gene was hypothesized to alter genetic susceptibility to alcohol dependence and alcohol-induced liver diseases. The aim of this study is to determine the association between aldehyde dehydrogenase 2 (rs671) glu504lys polymorphism and ALD. Methods: ALDH2 genotyping was performed in 535 healthy controls and 281 patients with ALD. Results: The prevalence of the common form of the single nucleotide polymorphism rs671, 504glu (glu/glu) was significantly higher in patients with ALD (95.4%) compared to that of controls (73.7%, P < 0.0001). Among controls, 23.7% had the heterozygous (glu/lys) genotype compared to 4.6% in those with ALD (odds ratio [OR] = 0.16, 95% CI: 0.09-0.28). The allele frequency for 504lys allele in patients with ALD was 2.3%, compared to 14.5% in healthy controls (OR = 0.13, 95% CI: 0.07-0.24). Conclusions: Patients with ALDH2 504lys variant were less associated with ALD compared to those with ALDH2 504glu using both genotypic and allelic analyses.

KW - Alcoholic liver disease

KW - Aldehyde dehydrogenase

KW - Gene polymorphism

KW - Risk

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DO - 10.1016/j.amjms.2018.03.012

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JO - American Journal of the Medical Sciences

JF - American Journal of the Medical Sciences

SN - 0002-9629

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