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Genetic Factors Involved in the Development and Progression of Nonalcoholic Fatty Liver Disease.

ABSTRACT: PURPOSE:The aim of our study was to identify the possible involvement of adiponutrine polymorphysm and of human leukocyte antigens (HLA) in the development of non-alcoholic fatty liver disease (NAFLD). MATERIAL AND METHODS:We included in this study a total of 138 subjects with non-invasive diagnosis of non-alcoholic hepatic steatosis. The patatin-like phospholipase domain containing protein 3 (PNPLA3) rs738409 (adiponutrine) polymorphism was genotyped by allelic discrimination TaqMan PCR assay (5' nuclease assay), using predesigned TaqMan SNP Genotyping Assays. Class I and II HLA antigens were determined by the polymerase chain reaction sequence specific oligonucleotide method (ADN-PCR-SSO). The results were compared with the same data from the control group subjects. RESULTS:For PNPLA 3 polymorphism we found [CC] genotype in 82 subjects (59,42%), [GC] genotype in 45 (32,61%) and [GG] genotype in 11 subjects (7,97%). The frequency of minor [G] risk allele was 0.25. We found class I and II HLA antigens HLA A24, HLA B15, HLA DR15, HLA DR16, HLA DQ3 and HLA DQ5 more frequent in subjects with hepatic steatosis without any other risk factor and HLA-A2, HLA-32, HLA B18, HLA B49 and HLA B53 in patients with obesity or metabolic syndrome. CONCLUSIONS:Our results are consistent with the literature and show an association of PNPLA3 rs738409 polymorphism with hepatic steatosis. Regarding histocompatibility antigens, we studied for the first time in our country the relationship between HLA and non-alcoholic fatty liver disease.

SUBMITTER: Amzolini AM

PROVIDER: S-EPMC6243520 | biostudies-literature | 2015 Oct-Dec

REPOSITORIES: biostudies-literature

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Project description:Nonalcoholic fatty liver disease (NAFLD) is common worldwide. The importance of genetic and epigenetic changes in etiology and pathogenesis of NAFLD has been increasingly recognized. However, the exact mechanism is largely unknown. A large number of single nucleotide polymorphisms (SNPs) related to NAFLD has been documented by candidate gene studies (CGSs). Among these genes, peroxisome proliferatoractivated receptor-?, adiponectin, leptin and tumor necrosis factor-? were frequently reported. Since the introduction of genome-wide association studies (GWASs), there have been significant advances in our understanding of genomic variations of NAFLD. Patatin-like phospholipase domain containing family member A3 (PNPLA3, SNP rs738409, encoding I148M), also termed adiponutrin, has caught most attention. The evidence that PNPLA3 is associated with increased hepatic fat levels and hepatic inflammation has been validated by a series of studies. Epigenetic modification refers to phenotypic changes caused by an adaptive mechanism unrelated to alteration of primary DNA sequences. Epigenetic regulation mainly includes microRNAs (miRs), DNA methylation, histone modifications and ubiquitination, among which miRs are studied most extensively. miRs are small natural single stranded RNA molecules regulating mRNA degradation or translation inhibition, subsequently altering protein expression of target genes. The miR-122, a highly abundant miR accounting for nearly 70% of all miRs in the liver, is significantly under-expressed in NAFLD subjects. Inhibition of miR-122 with an antisense oligonucleotide results in decreased mRNA expression of lipogenic genes and improvement of liver steatosis. The investigation into epigenetic involvement in NAFLD pathogenesis is just at the beginning and needs to be refined. This review summarizes the roles of genetics and epigenetics in the development of NAFLD. The progress made in this field may provide novel diagnostic biomarkers and therapeutic targets for NAFLD management.

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Genetic Factors Involved in the Development and Progression of Nonalcoholic Fatty Liver Disease.

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