학술논문

Association between PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), GCKR (rs780094), and elevated transaminase levels in overweight/obese Mexican adults
Document Type
article
Source
Molecular Biology Reports. 43(12)
Subject
Biochemistry and Cell Biology
Biological Sciences
Genetics
Clinical Research
Obesity
Aetiology
2.1 Biological and endogenous factors
Metabolic and endocrine
Adaptor Proteins
Signal Transducing
Adult
Alanine Transaminase
Aspartate Aminotransferases
Case-Control Studies
Female
Gene Frequency
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Lipase
Lysophospholipase
Male
Membrane Proteins
Mexico
Middle Aged
Overweight
Polymorphism
Single Nucleotide
Protein Phosphatase 1
Alanine aminotransferase
Aspartate aminotransferase
Candidate gene study
Latinos
Mexican adults
Nonalcoholic fatty liver disease
Biochemistry & Molecular Biology
Biochemistry and cell biology
Language
Abstract
There is scarce information about the link between specific single-nucleotide polymorphisms (SNPs) and risk of liver disease among Latinos, despite the disproportionate burden of disease among this population. Our aim was to investigate nine SNPs in or near the following genes: PNPLA3, LYPLAL1, PPP1R3B, GCKR, NCAN, IRS1, PPARG, and ADIPOR2 and examine their association with persistently elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels in Mexican adults. Data and samples were collected from 741 participants in the Mexican Health Worker Cohort Study, in Cuernavaca, Mexico. We identified 207 cases who had persistently elevated levels of ALT or AST (≥40 U/L) and 534 controls with at least two consecutive normal ALT or AST results in a 6 month period, during 2004-2006 and 2011-2013. TaqMan assays were used to genotype the SNPs. The risk allele of PNPLA3 rs738409 was found to be associated with persistently elevated levels of ALT or AST, adjusting for age, sex, BMI, type 2 diabetes, and ancestry: (OR 2.28, 95 % CI 1.13, 4.58). A significant association was found between the LYPLAL1, PPP1R3B, and GCKR risk alleles and elevated ALT or AST levels among overweight/obese adults. These results suggest that among Mexicans, the PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) polymorphisms may be associated with a greater risk of chronic liver disease among overweight adults. This study is the first to examine these nine SNPs in a sample of adults in Mexico.