title: Association with Spontaneous Hepatitis C Viral Clearance and Genetic Differentiation of IL28B/IFNL4 Haplotypes in Populations from Mexico.
abstract: OBJECTIVE
  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 r2 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.
authors.affiliation: Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, "Fray Antonio Alcalde", Guadalajara, Jalisco Mexico and Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.
authors.forename: Karina
authors.initials: K
authors.lastname: Gonzalez-Aldaco
authors.affiliation: Albert Einstein Medicina Diagnóstica, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.|Laboratorio de Gastroenterologia e Hepatologia Tropical. Instituto de Medicina Tropical, Departamento de Gastroenterologia, Faculdade da Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: João R
authors.initials: JR
authors.lastname: Rebello Pinho
authors.affiliation: Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, "Fray Antonio Alcalde", Guadalajara, Jalisco Mexico and Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.
authors.forename: Sonia
authors.initials: S
authors.lastname: Roman
authors.affiliation: Departamento de Patologia Clínica e Anatomia Patológica, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
authors.forename: Ketti
authors.initials: K
authors.lastname: Gleyzer
authors.affiliation: Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, "Fray Antonio Alcalde", Guadalajara, Jalisco Mexico and Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.
authors.forename: Nora A
authors.initials: NA
authors.lastname: Fierro
authors.affiliation: Albert Einstein Medicina Diagnóstica, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
authors.forename: Leticia
authors.initials: L
authors.lastname: Oyakawa
authors.affiliation: Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, "Fray Antonio Alcalde", Guadalajara, Jalisco Mexico and Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.
authors.forename: Omar
authors.initials: O
authors.lastname: Ramos-Lopez
authors.affiliation: Albert Einstein Medicina Diagnóstica, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
authors.forename: Rubia A
authors.initials: RA
authors.lastname: Ferraz Santana
authors.affiliation: Albert Einstein Medicina Diagnóstica, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
authors.forename: Roberta
authors.initials: R
authors.lastname: Sitnik
authors.affiliation: Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, "Fray Antonio Alcalde", Guadalajara, Jalisco Mexico and Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.
authors.forename: Arturo
authors.initials: A
authors.lastname: Panduro
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression / Q000276:immunology; D005787:Gene Frequency; D006239:Haplotypes; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006801:Humans; D007198:Indians, North American; D007372:Interferons; D007378:Interleukins / Q000235:genetics* / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000821:virology; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D012075:Remission, Spontaneous; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579163:IFNL4 protein, human