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Genome-wide association of IL28B with response to pegylated interferon-α and ribavirin therapy for chronic hepatitis C

Mizokami, Masashi ; Tanaka, Yasuhito ; Nishida, Nao ; Sugiyama, Masaya ; Kurosaki, Masayuki ; Matsuura, Kentaro ; Sakamoto, Naoya ; Nakagawa, Mina ; Korenaga, Masaaki ; Hino, Keisuke ; Hige, Shuhei ; Ito, Yoshito ; Mita, Eiji ; Tanaka, Eiji ; Mochida, Satoshi ; Murawaki, Yoshikazu ; Honda, Masao ; Sakai, Akito ; Hiasa, Yoichi ; Nishiguchi, Shuhei ; Koike, Asako ; Sakaida, Isao ; Imamura, Masatoshi ; Ito, Kiyoaki ; Yano, Koji ; Masaki, Naohiko ; Sugauchi, Fuminaka ; Izumi, Namiki ; Tokunaga, Katsushi

Nature genetics, 2009-10, Vol.41 (10), p.1105-1109 [Periódico revisado por pares]

New York, NY: Nature Publishing Group

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Título:
Genome-wide association of IL28B with response to pegylated interferon-α and ribavirin therapy for chronic hepatitis C
Autor: Mizokami, Masashi ; Tanaka, Yasuhito ; Nishida, Nao ; Sugiyama, Masaya ; Kurosaki, Masayuki ; Matsuura, Kentaro ; Sakamoto, Naoya ; Nakagawa, Mina ; Korenaga, Masaaki ; Hino, Keisuke ; Hige, Shuhei ; Ito, Yoshito ; Mita, Eiji ; Tanaka, Eiji ; Mochida, Satoshi ; Murawaki, Yoshikazu ; Honda, Masao ; Sakai, Akito ; Hiasa, Yoichi ; Nishiguchi, Shuhei ; Koike, Asako ; Sakaida, Isao ; Imamura, Masatoshi ; Ito, Kiyoaki ; Yano, Koji ; Masaki, Naohiko ; Sugauchi, Fuminaka ; Izumi, Namiki ; Tokunaga, Katsushi
Assuntos: Alleles ; Antiviral Agents - therapeutic use ; Asian People - genetics ; Biological and medical sciences ; Care and treatment ; Chromosomes, Human, Pair 19 ; Dosage and administration ; Drug Combinations ; Female ; Fundamental and applied biological sciences. Psychology ; Genetic aspects ; Genetics of eukaryotes. Biological and molecular evolution ; Genome, Human ; Genome-Wide Association Study ; Haplotypes ; Health aspects ; Hepatitis C ; Hepatitis C, Chronic - drug therapy ; Hepatitis C, Chronic - genetics ; Hepatitis C, Chronic - virology ; Human viral diseases ; Humans ; Infectious diseases ; Interferon alpha ; Interferon-alpha - therapeutic use ; Interferons ; Interleukins - genetics ; Male ; Medical sciences ; Patient outcomes ; Polymorphism, Single Nucleotide ; Ribavirin ; Ribavirin - therapeutic use ; Risk factors ; Single nucleotide polymorphisms ; Treatment Outcome ; Viral diseases ; Viral hepatitis
É parte de: Nature genetics, 2009-10, Vol.41 (10), p.1105-1109
Descrição: The recommended treatment for patients with chronic hepatitis C, pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV), does not provide sustained virologic response (SVR) in all patients. We report a genome-wide association study (GWAS) to null virological response (NVR) in the treatment of patients with hepatitis C virus (HCV) genotype 1 within a Japanese population. We found two SNPs near the gene IL28B on chromosome 19 to be strongly associated with NVR (rs12980275, P = 1.93 × 10−13, and rs8099917, 3.11 × 10−15). We replicated these associations in an independent cohort (combined P values, 2.84 × 10−27 (OR = 17.7; 95% CI = 10.0-31.3) and 2.68 × 10−32 (OR = 27.1; 95% CI = 14.6-50.3), respectively). Compared to NVR, these SNPs were also associated with SVR (rs12980275, P = 3.99 × 10−24, and rs8099917, P = 1.11 × 10−27). In further fine mapping of the region, seven SNPs (rs8105790, rs11881222, rs8103142, rs28416813, rs4803219, rs8099917 and rs7248668) located in the IL28B region showed the most significant associations (P = 5.52 × 10−28-2.68 × 10−32; OR = 22.3-27.1). Real-time quantitative PCR assays in peripheral blood mononuclear cells showed lower IL28B expression levels in individuals carrying the minor alleles (P = 0.015).
Editor: New York, NY: Nature Publishing Group
Idioma: Inglês

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Genome-wide association of IL28B with response to pegylated interferon-α and ribavirin therapy for chronic hepatitis C

New York, NY: Nature Publishing Group

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