Evidence map›Paper›PMID 37589914›Full record

ArticleIndian journal of gastroenterology : official journal of the Indian Society of Gastroenterology2023

A study of genetic variants, genetic risk score and DNA methylation of PNPLA3 and TM6SF2 in alcohol liver cirrhosis.

Bhagyalakshmi Shankarappa, Jayant Mahadevan, Pratima Murthy, Meera Purushottam, Biju Viswanath, Sanjeev Jain, Harshad Devarbhavi, Ashok Mysore V

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Article in Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
0.2field-weighted citation impact, top 42% of its field
1 · What the graph read from it

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3 · Its place in the literature

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2 citing papers in PubMed, 1 citations in OpenAlex.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Bhagyalakshmi ShankarappaDepartment of Psychiatry, St John's Medical College Hospital, Bengaluru 560 034, India.
Jayant MahadevanDepartment of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, 560 030, India.
Pratima MurthyDepartment of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, 560 030, India.
Meera PurushottamMolecular Genetics Laboratory, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, 560 030, India. meera.purushottam@gmail.com.
Biju ViswanathMolecular Genetics Laboratory, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, 560 030, India.
Sanjeev JainDepartment of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, 560 030, India.
Harshad DevarbhaviDepartment of Gastroenterology, St John's Medical College Hospital, Bengaluru, 560 034, India.
Ashok Mysore VDepartment of Psychiatry, St John's Medical College Hospital, Bengaluru 560 034, India.
National Institute of Mental Health and Neurosciences · INSt.John's Medical College Hospital · IN

Funding

Department of Biotechnology, Ministry of Science and Technology, India DBT/PR17316/MED/31/326/2015Indian Council of Medical Research 3/1/3/42/M/2014-NCD-IThe Wellcome Trust DBT India Alliance IA/CPHI/20/1/505266
6 · The paper itself

Abstract

backgroundGenetic and epigenetic factors are associated with the development of alcohol-associated liver disease (AALD). The single nucleotide polymorphisms (SNPs), rs738409 in Patatin-like phospholipase domain-containing protein (PNPLA3) and rs58542926 in Transmembrane 6 Superfamily Member 2 (TM6SF2) are strongly associated with AALD in different global populations, Hence, we analyzed the genetic risk score for these variants and deoxyribonucleic acid (DNA) methylation levels of the PNPLA3 and TM6SF2 genes among cases (alcohol liver cirrhosis) and controls (heavy drinkers without cirrhosis).

methodWe studied patients with alcohol use disorder (AUD) with cirrhosis (AUD-C + ve, n = 136) and without cirrhosis (AUD-C-ve, n = 107) drawn from the clinical services of St. John's Medical College Hospital (SJMCH) (Gastroenterology and Psychiatry) and Centre for Addiction Medicine (CAM), National Institute of Mental Health and Neurosciences, (NIMHANS). Genotype data was generated for rs738409 (PNPLA3) and rs58542926 (TM6SF2) and used to calculate unweighted genetic risk score (uGRS) and weighted genetic risk scores (wGRS). DNA methylation levels were estimated by pyrosequencing at PNPLA3 and TM6SF2 loci.

resultsOverall we observed a significantly higher genetic risk score (weighted genetic risk score, wGRS) in individuals with alcohol use disorder compared to control population (p =  < 0.01). Further, uGRS and wGRS were associated with the diagnosis of cirrhosis, even after correcting for age of onset, quantity and frequency of drinking. We also found hypomethylation at CpG2 of TM6SF2 gene in AUD-C + ve compared to AUD-C-ve (P = 0.02).

conclusionWe found that a genetic risk score based on SNPs in the PNPLA3 and TM6SF2 genes was significantly associated with cirrhosis in patients with AUD, suggesting a potential utility in identifying patients at risk and providing pre-emptive interventions. These may include interventions that aim to alter DNA methylation, which may be one of the mechanisms through which elevated genetic risk may influence the development of cirrhosis.

Indexed as

AlcoholismNon-alcoholic Fatty Liver DiseaseDNA MethylationFibrosisGenetic Predisposition to DiseaseGenotypeHumansLiver CirrhosisLiver Cirrhosis, AlcoholicMembrane ProteinsPolymorphism, Single NucleotideMembrane ProteinsTM6SF2 protein, humanAlcoholic liver cirrhosisAlcohol use disorderDeoxyribonucleic acid (DNA)DNA methylationHuman geneticsPatatin-like phospholipase domain-containing 3 protein (PNPLA3)PCRPyrosequencingSingle nucleotide polymorphismTransmembrane 6 superfamily member 2 protein (TM6SF2)

Identifiers

PMID37589914
OpenAlexW4385897477

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.