Dataset Information

Genetic variants in COL13A1, ADIPOQ and SAMM50, in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population.

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is the accumulation of extra fat in liver cells not caused by alcohol. Elevated transaminase levels are common indicators of liver disease, including NAFLD. Previously, we demonstrated that PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) are associated with elevated transaminase levels in overweight/obese Mexican adults. We investigated the association between 288 SNPs identified in genome-wide association studies and risk of elevated transaminase levels in an admixed Mexican-Mestizo sample of 178 cases of NAFLD and 454 healthy controls. The rs2896019, rs12483959, and rs3810622 SNPs in PNPLA3 and rs1227756 in COL13A1 were associated with elevated alanine aminotransferase (ALT, ?40IU/L). A polygenic risk score (PRS) based on six SNPs in the ADIPOQ, COL13A1, PNPLA3, and SAMM50 genes was also associated with elevated ALT. Individuals carrying 9-12 risk alleles had 65.8% and 48.5% higher ALT and aspartate aminotransferase (AST) levels, respectively, than those with 1-4 risk alleles. The PRS showed the greatest risk of elevated ALT levels, with a higher level of significance than the individual variants. Our findings suggest a significant association between variants in COL13A1, ADIPOQ, SAMM50, and PNPLA3, and risk of NAFLD/elevated transaminase levels in Mexican adults with an admixed ancestry. This is the first study to examine high-density single nucleotide screening for genetic variations in a Mexican-Mestizo population. The extent of the effect of these variations on the development and progression of NAFLD in Latino populations requires further analysis.

SUBMITTER: Larrieta-Carrasco E

PROVIDER: S-EPMC6027652 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Genetic variants in COL13A1, ADIPOQ and SAMM50, in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population.

Larrieta-Carrasco Elena E Flores Yvonne N YN Macías-Kauffer Luis R LR Ramírez-Palacios Paula P Quiterio Manuel M Ramírez-Salazar Eric G EG León-Mimila Paola P Rivera-Paredez Berenice B Cabrera-Álvarez Guillermo G Canizales-Quinteros Samuel S Zhang Zuo-Feng ZF López-Pérez Tania V TV Salmerón Jorge J Velázquez-Cruz Rafael R

Experimental and molecular pathology 20180104 1

Non-alcoholic fatty liver disease (NAFLD) is the accumulation of extra fat in liver cells not caused by alcohol. Elevated transaminase levels are common indicators of liver disease, including NAFLD. Previously, we demonstrated that PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) are associated with elevated transaminase levels in overweight/obese Mexican adults. We investigated the association between 288 SNPs identified in genome-wide association studies and ri ...[more]

PMID: 29307798

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Project description:For most of the world, human genome structure at a population level is shaped by interplay between ancient geographic isolation and more recent demographic shifts, factors that are captured by the concepts of biogeographic ancestry and admixture, respectively. The ancestry of non-admixed individuals can often be traced to a specific population in a precise region, but current approaches for studying admixed individuals generally yield coarse information in which genome ancestry proportions are identified according to continent of origin. Here we introduce a new analytic strategy for this problem that allows fine-grained characterization of admixed individuals with respect to both geographic and genomic coordinates. Ancestry segments from different continents, identified with a probabilistic model, are used to construct and study "virtual genomes" of admixed individuals. We apply this approach to a cohort of 492 parent-offspring trios from Mexico City. The relative contributions from the three continental-level ancestral populations-Africa, Europe, and America-vary substantially between individuals, and the distribution of haplotype block length suggests an admixing time of 10-15 generations. The European and Indigenous American virtual genomes of each Mexican individual can be traced to precise regions within each continent, and they reveal a gradient of Amerindian ancestry between indigenous people of southwestern Mexico and Mayans of the Yucatan Peninsula. This contrasts sharply with the African roots of African Americans, which have been characterized by a uniform mixing of multiple West African populations. We also use the virtual European and Indigenous American genomes to search for the signatures of selection in the ancestral populations, and we identify previously known targets of selection in other populations, as well as new candidate loci. The ability to infer precise ancestral components of admixed genomes will facilitate studies of disease-related phenotypes and will allow new insight into the adaptive and demographic history of indigenous people.

Project description:IntroductionThe burden of non-alcoholic fatty liver disease (NAFLD) continues to disproportionately impact under-resourced communities in the U.S., particularly Mexican-origin populations. Genetic polymorphisms such as the rs738409 C/G variant in patatin-like phospholipase domain-containing 3 (PNPLA3) have been associated with higher prevalence of and progression along the NAFLD spectrum. This qualitative study conducted in the U.S. Southwest aimed to assess Mexican-origin men's experience receiving genetic testing for PNPLA3 risk carrier status.MethodsSemi-structured interviews were conducted with 17 Mexican-origin men whose NAFLD status and genetic predisposition were determined as part of a previous cross-sectional study. The interview guide included questions exploring participants' insights on how genetic risk status was delivered, how the information influenced their motivation for lifestyle modification to reduce NAFLD risk, and any knowledge sharing that occurred with family members after learning of their PNPLA3 risk status. Interviews were conducted and audio recorded in English (n = 6) and Spanish (n = 11) and uploaded into NVivo software for data analysis and interpretation. Guided by the Health Belief Model, a thematic analysis approach was used to identify primary themes.ResultsResults highlighted men's preference for receiving this type of genetic risk information through a letter sent to their homes. General comprehension of PNPLA3 risk status was deemed high and most men stated sharing their genetic predisposition to NAFLD with their immediate family members. Participants also indicated that family and awareness of this genetic risk acted as primary motivators for implementing behavior changes (e.g., diet, physical activity) toward the prevention of more severe liver conditions.DiscussionFindings from this qualitative study suggest the feasibility of communicating genetic risk for NAFLD among Mexican-origin men. Future strategies for the dissemination of genetic risk results among Mexican-origin individuals should consider familial and cultural appropriate strategies.

Dataset Information

Genetic variants in COL13A1, ADIPOQ and SAMM50, in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population.

Publications

Genetic variants in COL13A1, ADIPOQ and SAMM50, in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population.

Similar Datasets

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