title: Association between PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), GCKR (rs780094), and elevated transaminase levels in overweight/obese Mexican adults.
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.
authors.affiliation: Unidad de Investigación Epidemiológica y en Servicios de Salud, Instituto Mexicano del Seguro Social (IMSS), Blvd. Benito Juárez No. 31 Col. Centro, Cuernavaca, Morelos, Mexico. ynflores@ucla.edu.|UCLA Department of Health Policy and Management, Fielding School of Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA. ynflores@ucla.edu.
authors.forename: Yvonne N
authors.initials: YN
authors.lastname: Flores
authors.affiliation: Instituto Nacional de Medicina Genómica, Periférico Sur No. 4809, Col. Arenal Tepepan, Mexico, DF, Mexico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Velázquez-Cruz
authors.affiliation: Unidad de Investigación Epidemiológica y en Servicios de Salud, Instituto Mexicano del Seguro Social (IMSS), Blvd. Benito Juárez No. 31 Col. Centro, Cuernavaca, Morelos, Mexico.
authors.forename: Paula
authors.initials: P
authors.lastname: Ramírez
authors.affiliation: Unidad de Investigación Epidemiológica y en Servicios de Salud, Instituto Mexicano del Seguro Social (IMSS), Blvd. Benito Juárez No. 31 Col. Centro, Cuernavaca, Morelos, Mexico.|Instituto Nacional de Medicina Genómica, Periférico Sur No. 4809, Col. Arenal Tepepan, Mexico, DF, Mexico.
authors.forename: Manuel
authors.initials: M
authors.lastname: Bañuelos
authors.affiliation: UCLA Department of Epidemiology, Fielding School of Public Health, Los Angeles, CA, USA.
authors.forename: Zuo-Feng
authors.initials: ZF
authors.lastname: Zhang
authors.affiliation: Los Angeles County Department of Health Services, 313 Figueroa, Los Angeles, CA, USA.
authors.forename: Hal F
authors.initials: HF
authors.lastname: Yee
authors.affiliation: UCLA Department of Epidemiology, Fielding School of Public Health, Los Angeles, CA, USA.
authors.forename: Shen-Chih
authors.initials: SC
authors.lastname: Chang
authors.affiliation: Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.
authors.forename: Samuel
authors.initials: S
authors.lastname: Canizales-Quinteros
authors.affiliation: Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico.
authors.forename: Manuel
authors.initials: M
authors.lastname: Quiterio
authors.affiliation: Clínica de Hígado, IMSS Hospital General Regional con UMF 1, Av. Plan de Ayala 1201, Flores Magon, Cuernavaca, Morelos, Mexico.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Cabrera-Alvarez
authors.affiliation: Instituto Nacional de Medicina Genómica, Periférico Sur No. 4809, Col. Arenal Tepepan, Mexico, DF, Mexico.
authors.forename: Nelly
authors.initials: N
authors.lastname: Patiño
authors.affiliation: Unidad de Investigación Epidemiológica y en Servicios de Salud, Instituto Mexicano del Seguro Social (IMSS), Blvd. Benito Juárez No. 31 Col. Centro, Cuernavaca, Morelos, Mexico.|Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico.
authors.forename: Jorge
authors.initials: J
authors.lastname: Salmerón
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D001219:Aspartate Aminotransferases / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008245:Lysophospholipase / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008800:Mexico; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D050177:Overweight / Q000097:blood / Q000201:enzymology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D054645:Protein Phosphatase 1 / Q000235:genetics*; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D008049:Lipase; D008245:Lysophospholipase; D008565:Membrane Proteins; D054645:Protein Phosphatase 1; C485100:GCKR protein, human; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent; C561408:LYPLAL1 protein, human; C586823:PPP1R3B protein, human
keywords: Alanine aminotransferase (ALT); Aspartate aminotransferase (AST); Candidate gene study; Latinos; Mexican adults; Nonalcoholic fatty liver disease