Genetic association and gene-gene interaction reveal genetic variations in ADH1B, GSTM1 and MnSOD independently confer risk to alcoholic liver diseases in India

Authors

Neelanjana Roy, Institute of Post Graduate Medical Education & Research
Debanjali Dasgupta, Institute of Post Graduate Medical Education & Research
Indranil Mukhopadhyay, Indian Statistical Institute, Kolkata
Ankita Chatterjee, National Institute of Biomedical Genomics
Kausik Das, Institute of Post Graduate Medical Education & Research
Pradip Bhowmik, Agartala Government Medical College
Soumyajit Das, Institute of Post Graduate Medical Education & Research
Priyadarshi Basu, National Institute of Biomedical Genomics
Amal K. Santra, Institute of Post Graduate Medical Education & Research
Simanti Datta, Institute of Post Graduate Medical Education & Research
Gopal Krishna Dhali, Institute of Post Graduate Medical Education & Research
Abhijit Chowdhury, Institute of Post Graduate Medical Education & Research
Soma Banerjee, Institute of Post Graduate Medical Education & Research

Article Type

Research Article

Publication Title

PLoS ONE

Abstract

Genetic susceptibility is an important modifier of clinical outcome and natural history of progression in Alcoholic liver disease (ALD). While the significance of ethnicity in this evolution is very clear, subtle inter-individual genetic variant(s) might be important and thus we investigated those in an Indian population. Fourteen markers were genotyped within two alcohol metabolism genes [Alcohol dehydrogenase (ADH) gene clusters (ADH1B and ADH1C) and Aldehyde dehydrogenase (ALDH2)], one microsomal ethanol oxidizing enzyme cytochrome p450 (CYP2E1) and three oxidative stress response (OSR) genes (MnSOD, GSTT1 and GSTM1) among 490 Bengali individuals (322 ALD and 168 control) from Eastern and North- Eastern India and validation was performed in a new cohort of 150 Bengali patients including 100 ALD and 50 advanced non-alcoholic steatohepatitis (NASH). Out of 14 genetic variants, carriage of 5 genotypes (rs2066701CC in ADH1B, rs1693425TT in ADH1C, rs4880TT in MnSOD and GSTT1/GSTM1 null, p-value <0.05) were noted significantly higher among ALD patients while inter or intra group gene-gene interaction analysis revealed that addition of risk genotype of any OSR gene enhanced the possibility of ALD synergistically. Multiple logistic regression analysis showed independent association of rs2066701CC, rs4880TT and GSTM1 null genotype with ALD while lower frequencies of those genotypes in advanced NASH patients further confirmed their causal relation to ALD. Thus these findings suggest that the three variants of ADH1C, MnSOD and GSTM1 can be used to identify individuals who are at high risk to develop ALD and may be helpful in proper management of Indian alcoholics.

DOI

10.1371/journal.pone.0149843

Publication Date

3-1-2016

Comments

Open Access; Gold Open Access

Recommended Citation

Roy, Neelanjana; Dasgupta, Debanjali; Mukhopadhyay, Indranil; Chatterjee, Ankita; Das, Kausik; Bhowmik, Pradip; Das, Soumyajit; Basu, Priyadarshi; Santra, Amal K.; Datta, Simanti; Dhali, Gopal Krishna; Chowdhury, Abhijit; and Banerjee, Soma, "Genetic association and gene-gene interaction reveal genetic variations in ADH1B, GSTM1 and MnSOD independently confer risk to alcoholic liver diseases in India" (2016). Journal Articles. 4228.
https://digitalcommons.isical.ac.in/journal-articles/4228