rs8099917

This study examined associations between IL-28B SNP rs8099917 and interferon therapy response in 19 patients with hepatitis C virus genotype 3a. While IL-28B genotype showed no significant association with sustained virological response (P=0.5232), a glutamic acid at position 72 in the HCV core region (E-type) was strongly associated with treatment response (80% response rate vs 0% for non-E-type, P=0.009). This is the first evaluation of IL-28B variation and HCV core region mutations in genotype 3a infections.

This association study examined IL28B polymorphisms in 220 Pakistani HCV patients (100 responders, 120 nonresponders) to pegylated interferon-alpha and ribavirin treatment. The rs12980275 AA genotype showed the strongest association with treatment response (62% responders vs 37.5% nonresponders, OR: 4.1, P < 0.0001), followed by rs12979860 CT (OR: 3.0, P < 0.001) and rs8099917 TT (P < 0.032). This was the first report describing rs12980275 association with HCV treatment response in Pakistani patients.

This functional study investigated the role of BDCA3+ dendritic cells in hepatitis C virus (HCV) innate immunity and found that these cells are potent producers of interferon-lambda 3 (IL-28B) in response to HCV. Crucially, subjects with the IL-28B major genotype rs8099917 TT produced significantly higher IL-28B levels upon HCV stimulation compared to minor genotype TG carriers (p < 0.05), establishing a mechanistic link between the IL-28B rs8099917 polymorphism and HCV-induced interferon response.

This comprehensive review examines the genetic background of nonalcoholic fatty liver disease (NAFLD), focusing on variants identified by genome-wide association studies (GWAS) and candidate gene studies. The most significant GWAS-identified variants are PNPLA3 rs738409 (I148M), which strongly associates with increased liver steatosis, fibrosis severity, and HCC risk (12-fold increased risk for homozygous carriers), and TM6SF2 rs58542926 (E167K), which increases NASH progression but reduces cardiovascular risk. The review also discusses numerous candidate genes involved in lipid and glucose metabolism and liver injury mechanisms.

This is a comprehensive journal compilation containing multiple oncology and pharmacogenomics studies published in 2013 across various journals. The collection includes 60+ papers covering cancer treatment outcomes, genetic polymorphisms predicting chemotherapy response and survival, pharmacogenetic variants in drug metabolism and DNA repair genes, and prognostic biomarkers in various cancer types including breast, lung, colorectal, hematologic malignancies, and others. Key findings include associations of XRCC1 variants (rs915927, rs76507, rs2854501, rs2854509, rs3213255) with bladder cancer chemotherapy survival, ABCG2 rs2725264 with lung cancer overall survival (HR 3.22), SLCO1B1 rs4149056 with methotrexate pharmacokinetics, MTHFR rs1801131 with acute lymphoblastic leukemia outcome, and ABCC3/GSTM variants with acute myeloid leukemia survival.

Multicenter study of 293 Japanese patients with HCV genotype 1b found that week 4 HCV RNA reduction is a strong predictor of sustained virologic response (SVR) to peginterferon-ribavirin therapy, with AUROC 0.927 (88% sensitivity, 87% specificity). The IL28B rs8099917 polymorphism and HCV viral factors (core region position 70 and ISDR) significantly influence the optimal cut-off thresholds for SVR prediction; patients with unfavorable TG/GG genotype require markedly lower viral reduction thresholds.

This document is a comprehensive collection of ~1,200 cancer-related research abstracts and summaries published in various journals (2013), covering clinical trials, pharmacogenomic studies, and mutation analyses across multiple cancer types including colorectal, breast, lung, lymphoma, and other malignancies. The collection documents associations between genetic variants (SNPs and somatic mutations), gene expression patterns, and cancer treatment outcomes, including studies on KRAS, EGFR, TP53, BRAF, and pharmacogenomic variants like CYP3A4 and UGT1A1.

Model incorporating the ITPA genotype (rs1127354) identifies patients at high risk of anemia and treatment failure with pegylated-interferon plus ribavirin therapy for chronic hepatitis C. In 446 genotype 1b HCV patients, ITPA CC genotype combined with baseline hemoglobin <14.0 g/dl predicted 57% anemia incidence, while patients with ITPA AA/CA and hemoglobin ≥14.0 g/dl had only 17% incidence. High-risk anemia was a significant negative predictor of sustained virological response.

This methods paper describes a rapid PCR-based test for screening IL28B SNPs (rs12979860 and rs8099917) and characterizes their distribution in a French Canadian injection drug user cohort (N=183). The study found that French Canadians have unusual genetic characteristics: high prevalence of responder genotypes (rs12979860 C/C: 51.4%, rs8099917 T/T: 63.4%) and reduced linkage disequilibrium between the two SNPs (|d'|=0.68, r=0.59), attributed to a founder effect from early French colonization.

This study evaluated add-on therapy with pitavastatin and eicosapentaenoic acid (EPA) combined with peginterferon and ribavirin for chronic hepatitis C 1b treatment. In patients with HCV-1b, the add-on group achieved significantly higher sustained virological response rates (54.7%) compared to standard therapy (30.1%, P<0.0001). Patients with IL-28B rs8099917 TT genotype had better responses overall, while those with TG+GG genotype benefited markedly from add-on therapy (37.9% vs 5.6%, P=0.007). IL-28B genotype remained the strongest independent predictor in multivariate analysis (OR 6.69, P=0.0019).

This case-control study of 330 subjects (154 HBV-related HCC patients, 86 chronic hepatitis B patients, 43 HBV self-limited infections, and 47 controls) examined three IL28B SNPs for association with hepatitis B-related hepatocellular carcinoma. The CC genotype at rs12979860 was protective (91.5% in controls vs 72.9% in CHB, P=0.01; vs 74.7% in HCC, P=0.01), while T allele carriers had increased HCC risk (χ²=4.44, P=0.04). Gene-gene interactions between rs12979860 and rs12980275 showed an OR of 11.79 (P=0.04), indicating IL28B polymorphisms influence HBV infection progression and HCC susceptibility.

This study evaluated IL28B SNP polymorphisms (rs12979860 and rs8099917) as predictors of treatment response in 100 Egyptian chronic hepatitis C (genotype 4) patients treated with pegylated interferon and ribavirin. The CC genotype of rs12979860 was associated with 87.2% sustained virological response (SVR) compared to 10% for TT (p<0.001), and rs8099917 TT was associated with 80.4% SVR versus 16.7% for GG, supporting IL28B polymorphisms as important biomarkers for predicting HCV treatment outcomes in genotype 4 patients.

This study of 272 Japanese patients with HCV genotype 1b investigated whether early viral dynamics (HCV RNA reduction at 4 and 12 weeks) retain predictive value for sustained virologic response (SVR) when stratified by IL28B polymorphisms (rs8099917, rs12979860). Among patients with favorable TT genotype for rs8099917, ≥3 log10 reduction in HCV RNA at 4 weeks predicted SVR (P<0.0001); conversely, TG/GG genotype patients showed no such prediction. Lack of early virologic response at 12 weeks retained strong predictive value for treatment failure regardless of IL28B genotype.

In 381 Japanese patients with HCV genotype 2 treated with 24-week interferon plus ribavirin combination therapy, IL28B rs8099917 genotype TG+GG was identified as an independent predictor of non-sustained virological response (P=0.017, OR=3.95). Sustained virological response was achieved in 81.6% overall, with multivariate analysis identifying younger age, higher albumin, absence of prior IFN therapy, and lower viral load as additional significant predictors of treatment success.

This study examined how the IL28B rs12979860 SNP polymorphism affects hepatitis C viral evolution during pegylated interferon and ribavirin treatment. Among 33 HCV genotype 1-infected patients, those with the favorable CC genotype showed significantly higher non-synonymous substitution rates (dN values) by day 7 of treatment and more amino acid substitutions in the NS5A region at baseline compared to non-CC patients, despite similar baseline viral loads and genetic diversity.

This case-control study investigated the association between IL28B gene polymorphisms and hepatitis B infection in a Chinese population from Yunnan. The authors screened three SNPs (rs12979860, rs8099917, and rs12980275) in 493 HBV-infected individuals and 460 controls. While no significant association was found between IL28B genetic polymorphisms and HBV infection susceptibility, the study identified associations between IL28B variants and leukomonocyte (LYM) levels in HBV-infected individuals, with rs12979860 showing significant differences in mean LYM levels (1.78 vs 2.00, p=0.032).

A comprehensive review of IL28B gene polymorphisms and their impact on drug responses across multiple conditions. The review discusses how three major IL28B SNPs (rs12979860, rs8099917, rs12980275) and seven additional polymorphisms predict treatment response to interferon-based therapies for chronic hepatitis C, hepatitis B, and myeloproliferative neoplasms. IL28B genotypes, particularly the favorable CC genotype at rs12979860 and TT genotype at rs8099917, are associated with higher sustained virologic response (SVR) rates in HCV treatment, with effect sizes showing 3-4.5 fold differences in relapse risk between genotypes.

This study examined IL28B genetic polymorphisms (rs12979860 and rs8099917) and hepatic ISG expression in 68 chronic hepatitis C patients, of whom 47 received interferon-ribavirin treatment. The rs12979860 CC genotype was significantly associated with sustained virological response (SVR; OR=6.29, 95% CI=1.72-23.01, P=0.004) and lower hepatic expression of IFI27, ISG15, and MX1 compared to CT-TT genotypes. IP10 expression was independently associated with SVR and strongly linked to liver fibrosis progression, while silencing of IP10 provided additional predictive value for treatment response.

Meta-analysis of 67 studies involving 20,163 patients for sustained virologic response (SVR) and 10 studies with 3,554 patients for spontaneous clearance (SC). IL28B polymorphisms showed strong associations with HCV clearance: rs12979860 (CC favorable) demonstrated similar associations across HCV genotypes and ethnicities (OR ~3.2-3.6), while rs8099917 (TT favorable) showed stronger effects in East Asians (OR ~6.3 vs 3.4 in Caucasians) and rs12980275 (AA favorable) had OR of 3.95 overall. All three SNPs showed genotype-dependent effects with HCV-1/4 having 3-fold higher ORs than HCV-2/3.

This study examined ITPA gene polymorphisms (rs1127354) and their influence on hemoglobin decreases during triple therapy with pegylated interferon, ribavirin, and telaprevir in 61 Japanese patients with hepatitis C virus genotype 1. Patients with the CC genotype at rs1127354 experienced significantly greater hemoglobin reductions (Δ-3.5 ± 1.1 g/dL at week 4, P=0.001) compared to CA/AA genotypes, required more RBV dose reductions during the first 12 weeks (52% vs 65% of target dose, P=0.039), and had higher risk for severe anemia (OR=36.8 for hemoglobin <11 g/dL). SVR rates were comparable between genotypes (71% vs 67%, P=0.736), demonstrating that with careful monitoring and dose adjustment, effective HCV treatment can be achieved despite genetic predisposition to RBV-induced anemia.

Comprehensive review of genetic background in nonalcoholic fatty liver disease (NAFLD). The PNPLA3 I148M variant (rs738409 C>G) is identified as a major genetic player strongly associated with increased liver fat content, NASH development, fibrosis severity, and HCC risk. The TM6SF2 E167K variant (rs58542926) emerges as another key contributor to NAFLD pathogenesis and disease progression. Multiple additional GWAS-identified variants and candidate genes are reviewed for their roles in NAFLD susceptibility and progression.

Retrospective study of 1,713 treatment-naive hepatitis C virus (HCV) genotype 3 patients developing and validating a clinical prediction score for sustained virologic response (SVR) to peginterferon alfa-2a/ribavirin therapy. The prediction score incorporating age, bodyweight, cirrhosis status, ALT level, platelet count, and HCV RNA achieved 87% SVR rate in patients with score ≥8. IL28B variants rs12979860 (CC) and rs8099917 (TT) were associated with virological response but not included in the final model due to data limitations.

This study examined IL-28B genetic variation and spontaneous hepatitis C virus clearance using multiple- and single-source cohorts. IL-28B protective haplotypes were strongly associated with HCV clearance (OR=2.1 [95% CI 1.6-3.0] in multiple-source cohort, OR=3.9 [95% CI 1.5-10.2] in single-source cohort; P=6×10⁻⁹). The protective haplotypes were in perfect linkage (r²=1.0) with the nonsynonymous coding variant rs8103142, and homozygosity for the rs12979860 C allele predicted the protective haplotype status.

This is a special issue of the Italian medical journal BeAdfiles (September 2012) dedicated to genetic conditioning in HIV and hepatitis virus infections. It reviews the major genetic polymorphisms that influence disease progression, treatment response, and drug toxicity in HIV and chronic hepatitis B and C infections, with particular emphasis on IL28B polymorphisms (rs809917 and others) predicting HCV treatment response to interferon-alpha and ribavirin therapy, and ITPA gene variants protecting against ribavirin-induced anemia. The issue also covers pharmacogenetic markers (CYP2B6, ABCB1, HLA-B*5701) and their clinical applications in antiretroviral therapy.

Population genetics study investigating IFNL3/IFNL4 interferon gene polymorphisms in 669 HCV patients and 1,520 healthy controls across Caucasian and Mongoloid ethnic groups in Russia and Mongolia. Spontaneous HCV viral clearance was significantly more frequent in the Mongoloid population, with protective genotypes: CC genotype at rs12979860, TT genotype at rs8099917, and TT/TT genotype at rs368234815.

This study examined 156 patients with chronic hepatitis C to investigate genetic polymorphisms near the IL28B gene (rs8099917) and HCV core region amino acid substitutions (residue 70: arginine vs. glutamine) as factors influencing interferon sensitivity. The rs8099917 TT genotype showed significantly greater HCV RNA reduction after standard interferon administration compared to TG/GG genotypes (1.56 ± 0.46 vs 0.95 ± 0.66 log10 IU/ml at 24 hr, P<0.0001), and was independently associated with sustained virologic response to peginterferon-ribavirin combination therapy (48.6% in TT vs 8.3% in TG/GG, P=0.0010).

A clinical study of 274 Japanese patients with HCV genotype 1b examined whether peginterferon/ribavirin combination therapy induces mutations at HCV core region residue 70 and whether IL28B genetic polymorphism (rs8099917) affects this mutation. The study found that therapy does not induce de novo mutations at this residue regardless of IL28B genotype; observed mutations were due to selection of pre-existing strains. Patients with the TT genotype at rs8099917 had significantly higher rates of wild-type amino acid (82.2% vs 52.8%, p<0.0001) and superior sustained virologic response (53.0% vs 19.4%, p<0.0001) compared to TG/GG carriers.

In 133 chronic hepatitis C patients, the IL28B rs12979860 CC protective genotype was inversely associated with hepatic expression of interferon-stimulated genes (ISGs) that promote antiviral responses (ISG15: p=1.42E-12, MxA: p=6.40E-11) and positively associated with expression of genes that suppress antiviral signaling (A20: p=0.00107, Zc3h12a: p=0.00129). The rs12979860 genotype was significantly associated with HCV treatment response to peginterferon-ribavirin therapy, suggesting it affects treatment outcomes through altered intrahepatic ISG expression patterns.

This study examined the IL-28b gene polymorphism (rs8099917) in 183 liver transplant patients with recurrent hepatitis C virus infection, analyzing 605 protocol liver biopsies. The G allele was significantly associated with higher histological grades of inflammation (median grade 3.0 for GG, 2.5 for GT, 2.0 for TT; p<0.001), elevated aminotransferase levels (ALT p=0.001, AST p=0.003), and lack of response to interferon-based antiviral therapy (p<0.001). The G allele was significantly less frequent among successfully treated patients and was not present in the GG genotype among responders, suggesting IL-28b polymorphisms may serve as markers for graft inflammation severity and predictors of antiviral treatment failure.

This study examined 136 chronic hepatitis C patients for the TLR7 rs179008/Gln11Leu SNP and found the variant T allele associated with portal lymphoid aggregates (P=0.013 in males, P=0.032) and significantly lower hepatic IL-29/IFNλ1 expression (P=0.015) and IL-28 receptor expression. The T allele showed a trend toward reduced interferon-alpha treatment response (30% vs 63% response, P=0.069).

This functional association study investigated IL28B genotype as a determinant of intrahepatic interferon-stimulated gene (ISG) expression in 61 chronic hepatitis C patients. The protective IL28B CC genotype (rs12979860) was associated with significantly lower expression of ISGs (e.g., ISG15 3.9-fold lower, MX1 2.6-fold lower, p < 10⁻⁵) and higher expression of immunomodulatory genes like CXCL9 (3.3-fold). Treatment response was associated with IL28B genotype (p = 0.0054), though the non-synonymous variant Lys70Arg (rs8103142) showed no functional differences in vitro, suggesting non-coding regulatory variants drive the association.

A prospective cohort study of 163 individuals with recent hepatitis C virus (HCV) infection found that IL28B rs8099917 TT genotype independently predicted spontaneous HCV clearance (AHR 3.78, 95% CI 1.04-13.76, p=0.044) with 32% clearance in TT homozygotes versus 5% in GG/GT carriers. However, IL28B genotype did not impact treatment response (SVR 62% TT vs 64% GG/GT, p=0.884), suggesting IL28B may be useful for determining treatment timing but not for predicting response to therapy.

A case-control study in a Russian population (285 type 1 diabetes patients, 300 controls) examining 58 SNPs across 47 genes involved in fibrogenesis, endothelial dysfunction, and inflammation. Seven SNPs showed significant association with T1D susceptibility: rs3765124 (ADAMDEC1 AA genotype, OR=1.79, p=0.004), rs1007856 (ITGB5 TT genotype, OR=1.67, p=0.015), rs20579 (LIG1 CC genotype, OR=1.86, p=0.004), rs12980602 (IFNL2 allele C, OR=1.49, p=0.029), rs4986819 (PARP4 allele C, OR=1.52, p=0.044), rs1143674 (ITGA4 GG genotype, OR=2.06, p=0.002), and rs679620 (MMP3 AA genotype, OR=2.03, p=0.008).