Hypomethylation of Long Interspersed Nucleotide Elements and Aldehyde Dehydrogenase in Patients of Alcohol Use Disorder with Cirrhosis.

Alcohol use disorder (AUD) and cirrhosis are key outcomes of excessive alcohol use, and a genetic influence in these outcomes is increasingly recognized. While 80-90% of heavy alcohol users show evidence of fatty liver, only 10-20% progress to cirrhosis. There is currently no clear understanding of the causes of this difference in progression. The aim of this study is to evaluate genetics and epigenetics at the aldehyde dehydrogenase ( locus in patients with AUD and liver complications. Study participants were inpatients from the clinical services of Gastroenterology and Psychiatry at St. John's Medical College Hospital (SJMCH) and the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. Men diagnosed as having AUD with cirrhosis (AUDC+ve,  = 136) and AUD without cirrhosis (AUDC-ve,  = 107) were assessed. FibroScan/sonographic evidence was used to rule out fibrosis in the AUDC-ve group. Genomic DNA was used for genotyping at the (rs2238151) locus. A subset of 89 samples was used for DNA methylation (AUDC+ve,  = 44; and AUDC-ve,  = 45) analysis at long interspersed nucleotide element 1 () and cytosine-phosphate-guanine (CpG) loci by pyrosequencing. DNA methylation was significantly lower in the AUDC+ve group compared with the AUDC-ve group ( < 0.001). Lower methylation was associated with a risk allele (T) of the locus (rs2238151) ( = 0.01). Global () DNA methylation levels were also significantly lower in the AUDC+ve group compared with the AUDC-ve group ( = 0.01). Compromised global methylation ( and hypomethylation at the gene was observed in patients with cirrhosis compared with those without cirrhosis. DNA methylation could be explored as a biomarker for cirrhosis and liver complications.