Genetic polymorphism of IL28B in hepatitis C-infected haemophilia patients in Israel.
Single-nucleotide polymorphisms (SNPs) near the IL28B gene were identified as major predictors of treatment response (sustained virologic response--SVR) and spontaneous clearance of HCV. Haemophilia patients have the highest prevalence of HCV, and are a unique target for genetic studies. The Israeli population is ethnically heterogeneous; therefore, genetic variability is anticipated. To determine the IL28B haplotypes in HCV-infected haemophilia patients and association with SVR and spontaneous viral clearance. IL28B polymorphism at SNPs rs12979860 and rs8099917 was determined in sera obtained from 130 HCV-infected haemophilia patients. The frequency of the various haplotypes was analysed according to treatment response, spontaneous HCV clearance, viral load and degree of fibrosis. The CC haplotype at SNP rs12979860 was found in 31% of patients, whereas the TT genotype at SNP rs8099917 was detected in 57% of cases. SVR was achieved in 70% of patients carrying the CC haplotype (P = 0.0196 vs. CT/TT), and 50% of the TT genotype at SNP rs8099917 (P = 0.0227 vs. TG/GG). Thirty-five percent of patients carrying the CC haplotype and 26% with the TT genotype at SNP rs8099917 showed spontaneous clearance of HCV infection (P = 0.00262 vs. CT/TT; and P = 0.00371 vs. TG/GG respectively). The C-allele frequency was exceptionally high (71%) in immigrants from the Asian republics of Russia. In HCV-infected haemophilia patients, SVR was more commonly achieved among patients who had the CC (rs12979860) or TT (rs8099917) genotype. Likewise, patients who possess harbour the CC or TT genotypes were more likely to clear HCV infection spontaneously. A unique distribution of the CC genotype was observed in some ethnic groups.
Department of Gastroenterology and Hepatology, Sheba Medical Centre, Tel-Hashomer, Israel. yaakov@sheba.health.gov.il
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Maor
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Morali
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Bashari
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Pénaranda
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Schapiro
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Martinowitz
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Halfon
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D060085:Coinfection; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006467:Hemophilia A / Q000235:genetics* / Q000821:virology*; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D007557:Israel; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012074:Remission Induction; D012075:Remission, Spontaneous; D019562:Viral Load; D000095022:Interferon Lambda
D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda