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Association with Spontaneous Hepatitis C Viral Clearance and Genetic Differentiation of IL28B/IFNL4 Haplotypes in Populations from Mexico

AIM: To analyze the genetic heterogeneity of the Amerindian and admixed population (Mestizos) based on the IL28B (rs12979860, rs8099917) and IFNL4 (rs368234815) haplotypes, and their association with spontaneous clearance (SC) and liver damage in patients with hepatitis C infection from West Mexico....

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Autores principales: Gonzalez-Aldaco, Karina, Rebello Pinho, João R., Roman, Sonia, Gleyzer, Ketti, Fierro, Nora A., Oyakawa, Leticia, Ramos-Lopez, Omar, Ferraz Santana, Rubia A., Sitnik, Roberta, Panduro, Arturo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4704808/
https://www.ncbi.nlm.nih.gov/pubmed/26741362
http://dx.doi.org/10.1371/journal.pone.0146258
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author Gonzalez-Aldaco, Karina
Rebello Pinho, João R.
Roman, Sonia
Gleyzer, Ketti
Fierro, Nora A.
Oyakawa, Leticia
Ramos-Lopez, Omar
Ferraz Santana, Rubia A.
Sitnik, Roberta
Panduro, Arturo
author_facet Gonzalez-Aldaco, Karina
Rebello Pinho, João R.
Roman, Sonia
Gleyzer, Ketti
Fierro, Nora A.
Oyakawa, Leticia
Ramos-Lopez, Omar
Ferraz Santana, Rubia A.
Sitnik, Roberta
Panduro, Arturo
author_sort Gonzalez-Aldaco, Karina
collection PubMed
description AIM: To analyze the genetic heterogeneity of the Amerindian and admixed population (Mestizos) based on the IL28B (rs12979860, rs8099917) and IFNL4 (rs368234815) haplotypes, and their association with spontaneous clearance (SC) and liver damage in patients with hepatitis C infection from West Mexico. METHODS: A total of 711 subjects from West Mexico (181 Amerindians and 530 Mestizos) were studied for the prevalence of IL28B (rs12979860C/T, rs8099917G/T) and IFNL4 (rs368234815∆G/TT) genotypes. A case-control study was performed in 234 treatment-naïve HCV Mestizos (149 chronic hepatitis C and 85 with SC) for the association of haplotypes with SC and liver damage. A real-time PCR assay was used for genotyping, and transitional elastography staged liver damage. RESULTS: Significant Fst-values indicated differentiation between the studied populations. The frequencies of the protective C, T, TT alleles were significantly lower in the Amerindians than in Mestizos (p<0.05). The r(2) measure of linkage disequilibrium was significant for all variants and the T/G/ΔG risk haplotype predominated in Amerindians and secondly in Mestizos. The protective C/T/TT haplotype was associated with SC (OR = 0.46, 95% IC 0.22–0.95, p = 0.03) and less liver damage (OR = 0.32, 95% IC 0.10–0.97, p = 0.04) in chronic patients. The Structure software analysis demonstrated no significant differences in ancestry among SC and chronic patients. CONCLUSIONS: West Mexico´s population is genetically heterogeneous at the IL28B/IFNL4 polymorphisms. The T/G/ΔG high-risk haplotype predominated in Amerindians and the beneficial alternative haplotype in Mestizos. The C/T/TT haplotype was associated with SC and less liver damage in chronically infected Mestizo patients.
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spelling pubmed-47048082016-01-15 Association with Spontaneous Hepatitis C Viral Clearance and Genetic Differentiation of IL28B/IFNL4 Haplotypes in Populations from Mexico Gonzalez-Aldaco, Karina Rebello Pinho, João R. Roman, Sonia Gleyzer, Ketti Fierro, Nora A. Oyakawa, Leticia Ramos-Lopez, Omar Ferraz Santana, Rubia A. Sitnik, Roberta Panduro, Arturo PLoS One Research Article AIM: To analyze the genetic heterogeneity of the Amerindian and admixed population (Mestizos) based on the IL28B (rs12979860, rs8099917) and IFNL4 (rs368234815) haplotypes, and their association with spontaneous clearance (SC) and liver damage in patients with hepatitis C infection from West Mexico. METHODS: A total of 711 subjects from West Mexico (181 Amerindians and 530 Mestizos) were studied for the prevalence of IL28B (rs12979860C/T, rs8099917G/T) and IFNL4 (rs368234815∆G/TT) genotypes. A case-control study was performed in 234 treatment-naïve HCV Mestizos (149 chronic hepatitis C and 85 with SC) for the association of haplotypes with SC and liver damage. A real-time PCR assay was used for genotyping, and transitional elastography staged liver damage. RESULTS: Significant Fst-values indicated differentiation between the studied populations. The frequencies of the protective C, T, TT alleles were significantly lower in the Amerindians than in Mestizos (p<0.05). The r(2) measure of linkage disequilibrium was significant for all variants and the T/G/ΔG risk haplotype predominated in Amerindians and secondly in Mestizos. The protective C/T/TT haplotype was associated with SC (OR = 0.46, 95% IC 0.22–0.95, p = 0.03) and less liver damage (OR = 0.32, 95% IC 0.10–0.97, p = 0.04) in chronic patients. The Structure software analysis demonstrated no significant differences in ancestry among SC and chronic patients. CONCLUSIONS: West Mexico´s population is genetically heterogeneous at the IL28B/IFNL4 polymorphisms. The T/G/ΔG high-risk haplotype predominated in Amerindians and the beneficial alternative haplotype in Mestizos. The C/T/TT haplotype was associated with SC and less liver damage in chronically infected Mestizo patients. Public Library of Science 2016-01-07 /pmc/articles/PMC4704808/ /pubmed/26741362 http://dx.doi.org/10.1371/journal.pone.0146258 Text en © 2016 Gonzalez-Aldaco et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
spellingShingle Research Article
Gonzalez-Aldaco, Karina
Rebello Pinho, João R.
Roman, Sonia
Gleyzer, Ketti
Fierro, Nora A.
Oyakawa, Leticia
Ramos-Lopez, Omar
Ferraz Santana, Rubia A.
Sitnik, Roberta
Panduro, Arturo
Association with Spontaneous Hepatitis C Viral Clearance and Genetic Differentiation of IL28B/IFNL4 Haplotypes in Populations from Mexico
title Association with Spontaneous Hepatitis C Viral Clearance and Genetic Differentiation of IL28B/IFNL4 Haplotypes in Populations from Mexico
title_full Association with Spontaneous Hepatitis C Viral Clearance and Genetic Differentiation of IL28B/IFNL4 Haplotypes in Populations from Mexico
title_fullStr Association with Spontaneous Hepatitis C Viral Clearance and Genetic Differentiation of IL28B/IFNL4 Haplotypes in Populations from Mexico
title_full_unstemmed Association with Spontaneous Hepatitis C Viral Clearance and Genetic Differentiation of IL28B/IFNL4 Haplotypes in Populations from Mexico
title_short Association with Spontaneous Hepatitis C Viral Clearance and Genetic Differentiation of IL28B/IFNL4 Haplotypes in Populations from Mexico
title_sort association with spontaneous hepatitis c viral clearance and genetic differentiation of il28b/ifnl4 haplotypes in populations from mexico
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4704808/
https://www.ncbi.nlm.nih.gov/pubmed/26741362
http://dx.doi.org/10.1371/journal.pone.0146258
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