Interleukin 28B Gene Polymorphism and Association with Chronic Hepatitis C Therapy Results in Latvia

Abstract

Introduction. With the standard treatment of chronic hepatitis C, sustained virological response (SVR) can be achieved only in half of all patients. Interleukin-28B appears to be involved in the control of HCV infection, and the genetic polymorphism of the encoding IL-28B gene may determine the efficacy of clearance of HCV. The aim of this paper was to detect IL-28B gene polymorphism in Latvia and to analyze therapy results. This is the first study on IL-28B gene polymorphism in Latvia. Material and Methods. There were 159 chronic viral hepatitis C patients included in the study. In order to detect IL-28B gene polymorphism, we used molecular biology techniques and methods: classical DNA separation, amplification by PCR, and standard sequencing. Genotype was defined as CC, CT, TC, or TT type. 142 patients were treated with the standard of care treatment. Results were analyzed according to IL-28B polymorphism. Results. There were 53 patients (33%) with CC genotype, 84 patients (53%) with CT/TC genotype, and 22 patients (14%) with TT genotype. 34 patients (74%) in CC genotype subgroup achieved SVR versus 50 patients (52%) in non-CC subgroups. In patients with genotype 1, SVR was achieved in 16 patients (84%) in CC subgroup versus 30 patients (47.6%) in non-CC subgroups, P = 0.007. Conclusions. The most common genotype of IL28B in Latvia is CT/TC, with an incidence of 53%. Patients with CC genotype achieved SVR more often than CT or TT subgroups. IL28B gene polymorphism therefore is a strong predictor of treatment result.

Single nucleotide polymorphisms near IL28B gene and response to treatment of chronic hepatitis C in hemodialysis patients

“…The CC genotype of rs12979860, TT genotype of rs8099917, and AA genotype of rs12980275 were significantly associated with the successful treatment (p ¼ 0.001, p ¼ 0.016, and p ¼ 0.002, respectively). Similar associations between SVR and IL28B gene polymorphisms were evaluated in the studies of Sporea et al 32 and Tolmane et al, 33 although they identified only one polymorphism (rs12979860). The study of Sporea I et al included a cohort of 107 Caucasian (Romanian) patients infected with HCV genotype 1 treated with PEGIFN/RBV.…”

“…The study of Tolmane I et al included 142 Caucasian (Latvian) patients infected with HCV genotype 1 (61%) and HCV genotype 2 or 3 (39%) treated with PEGIFN/RBV. 33 The SVR rate was 59%, and it was significantly associated with the CC genotype of rs12979860 (p ¼ 0.002). The number of study participants is a limitation of the study.…”

Association of the Treatment Induced Clearance of Hepatitis C Virus Infection with the IL28B Gene Polymorphisms

“…The CC genotype of rs12979860, TT genotype of rs8099917, and AA genotype of rs12980275 were significantly associated with the successful treatment (p=0.001, p=0.016, and p=0.002, respectively) [18]. Similar SVR rates and association with the IL28B gene polymorphisms were evaluated in the studies of Sporea I et al [19] and Tolmane I et al [16], although they studied only the rs12979860 as SNP. The study of Sporea I et al included a cohort of 107 Caucasian (Romanian) patients infected with HCV genotype 1 treated with PEGIFN/RBV [19].…”

“…In Latvia, majority of the people are Caucasians, and they reported similar distribution of frequencies of rs12979860: CC in 33%, CT in 53% and TT in 14% of study participants (Caucasians, n=142) [16]. Similar to our findings, the distribution of frequencies of rs8099917 genotypes among study participants (Caucasians, n= 175) in the study of Sticchi L et al, was as follows: TT in 55%, TG in 40% and GG in 5% [17].…”

TGF-β1 polymorphism 509 C>T is associated with an increased risk for hepatocellular carcinoma in HCV-infected patients

“…Only a fraction of infected patients develop HCC during their lifetime, suggesting that the etiology of HCC is poorly understood (El-Serag, 2011). Several factors, such as viral kinetics, immune mechanisms, environmental factors, and genetic factors, may be responsible for the various HCV-related outcomes (Tolmane et al, 2012). Increasing evidence suggests that genetic factors contribute to HCC development.…”