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

Author(s)

Gonzalez-Aldaco, Karina ^{[1, 2]} ; Rebello Pinho, Joao R. ^{[3, 4]} ; Roman, Sonia ^{[1, 2]} ; Gleyzer, Ketti ^[5] ; Fierro, Nora A. ^{[1, 2]} ; Oyakawa, Leticia ^[3] ; Ramos-Lopez, Omar ^{[1, 2]} ; Santana, Rubia A. Ferraz ^[3] ; Sitnik, Roberta ^[3] ; Panduro, Arturo ^{[1, 2]}

Affiliation

^[1] Civil Hosp Guadalajara, Dept Mol Biol Med, Guadalajara, Jalisco - Mexico

^[2] Univ Guadalajara, Hlth Sci Ctr, Guadalajara 44430, Jalisco - Mexico

^[3] Hosp Israelita Albert Einstein, Albert Einstein Med Diagnost, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Fac Med, Dept Gastroenterol, Lab Gastroenterol & Hepatol Trop, Inst Med Trop, Sao Paulo, SP - Brazil

^[5] Hosp Israelita Albert Einstein, Dept Patol Clin & Anat Patol, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: PLoS One; v. 11, n. 1 JAN 7 2016.
• Web of Science Citations: 14

Abstract

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 caseq-control study was performed in 234 treatmentq-naive HCV Mestizos (149 chronic hepatitis C and 85 with SC) for the association of haplotypes with SC and liver damage. A realq-time PCR assay was used for genotyping, and transitional elastography staged liver damage. Results Significant Fstq-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/Delta G risk haplotype predominated in Amerindians and secondly in Mestizos. The protective C/T/TT haplotype was associated with SC (OR = 0.46, 95% IC 0.22q-0.95, p = 0.03) and less liver damage (OR = 0.32, 95% IC 0.10q-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/Delta G 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. (AU)

• FAPESP's process: 10/10549-1 - IL-28 gene single nucleotide polymorphisms (SNPs) genotyping in individuals infected with Hepatitis C virus
• Grantee: João Renato Rebello Pinho
• Support Opportunities: Regular Research Grants