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Association between PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), GCKR (rs780094), and elevated transaminase levels in overweight/obese Mexican adults

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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.

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Acknowledgments

This research was supported by Grants from the Instituto Mexicano del Seguro Social (IMSS), Instituto Nacional de Medicina Genomica (INMEGEN) Grant #119-11/2012/I, and the Consejo Nacional de Ciencia y Tecnología (CONACyT) Grants #26267 M and SALUD-2011-01-161930. Dr. Flores received a Grant from the American Association for the Study of Liver Disease (AASLD) to support her work on this study, and was also supported by NIH/NCI K07CA197179. The authors express their gratitude to the Mexican Health Worker Cohort Study participants, their families, and the IMSS clinicians and staff.

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Authors and Affiliations

  1. 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

    Yvonne N. Flores, Paula Ramírez, Manuel Bañuelos & Jorge Salmerón

  2. UCLA Department of Health Policy and Management, Fielding School of Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA

    Yvonne N. Flores

  3. Instituto Nacional de Medicina Genómica, Periférico Sur No. 4809, Col. Arenal Tepepan, Mexico, DF, Mexico

    Rafael Velázquez-Cruz, Manuel Bañuelos & Nelly Patiño

  4. UCLA Department of Epidemiology, Fielding School of Public Health, Los Angeles, CA, USA

    Zuo-Feng Zhang & Shen-Chih Chang

  5. Los Angeles County Department of Health Services, 313 Figueroa, Los Angeles, CA, USA

    Hal F. Yee Jr.

  6. Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico

    Samuel Canizales-Quinteros

  7. Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico

    Manuel Quiterio & Jorge Salmerón

  8. Clínica de Hígado, IMSS Hospital General Regional con UMF 1, Av. Plan de Ayala 1201, Flores Magon, Cuernavaca, Morelos, Mexico

    Guillermo Cabrera-Alvarez

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  1. Yvonne N. Flores
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  2. Rafael Velázquez-Cruz
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  3. Paula Ramírez
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  4. Manuel Bañuelos
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  8. Samuel Canizales-Quinteros
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  9. Manuel Quiterio
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Correspondence to Yvonne N. Flores.

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Flores, Y.N., Velázquez-Cruz, R., Ramírez, P. et al. Association between PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), GCKR (rs780094), and elevated transaminase levels in overweight/obese Mexican adults. Mol Biol Rep 43, 1359–1369 (2016). https://doi.org/10.1007/s11033-016-4058-z

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