The relationship between serum concentration of interleukin-35 and foxp3 polymorphism in patients undergoing coronary artery bypass graft surgery

Abstract Objective: To investigate the association between interleukin-35 (IL-35) levels and single nucleotide polymorphisms (rs3761548, rs3761547) of the FoxP3 gene in coronary artery bypass grafting (CABG) patients. Methods: We conducted a prospective study including 140 patients, who were scheduled for elective isolated on-pump CABG with cardiopulmonary bypass (CPB) from January 2017 to September 2018 in the Jorjani heart center. Blood samples were collected before and 12 hours after the operation. Serum levels of IL-35 were measured by enzyme-linked immunosorbent assay and the pattern of genetic variations was assessed using single specific primer-polymerase chain reaction. Results: The serum concentrations of IL-35 after surgery were significantly higher than pre-surgery levels (18.4±8.3 vs. 9.89±3.2, respectively, P=0.002). There was no significant association between genotype frequencies of rs3761548 and rs3761547 and elevated IL-35 levels (P>0.05). There were significant associations between IL-35 levels and preoperative variables, including age (r=-0.34, P=0.047) and body mass index (r=-0.41, P=0.045), and intraoperative variables, including CPB time (r=0.4, P=0.02) and mean arterial pressure (r=-0.38, P=0.046), in carriers of the rs3761548 AA genotype. Conclusion: Serum IL-35 concentrations were significantly increased in CPB patients, which may contribute to the post-CPB compensatory anti-inflammatory response syndrome. IL-35 increased levels were not influenced by FoxP3 promoter polymorphisms (rs3761548, rs3761547).

Lack of association between mutation in IL36RN and palmoplantar pustular psoriasis in Chinese patients

Abstract Background: Palmoplantar pustulosis is considered to be a localized pustular psoriasis confined to the palms and soles. Mutation of the IL36RN gene, encoding interleukin-36 receptor antagonist (IL-36Ra), is associated with generalized pustular psoriasis, but IL36RN mutations in Chinese palmoplantar pustulosis patients have not previously been investigated. Objective: The aim of this study was to evaluate the mutation of IL36RN in Chinese patients with palmoplantar pustulosis. Methods: Fifty-one Han Chinese patients with palmoplantar pustulosis were recruited. All exons and exon-intron boundary sequences of IL36RN were amplified in polymerase chain reactions, and Sanger sequencing of the amplicons was performed. Results: Among the 51 palmoplantar pustulosis patients, four different single-base substitutions were identified in nine patients. The mutations were c.140A>G/p.Asn47Ser in five patients, c.258G>A/p.Met86IIe in two patients, and c.115+6T>C and c.169G>A/p.Val57IIe in one patient each. All mutations were heterozygous. Comparison with the human genome database and reported literature suggested that these variants may not be pathogenic mutations causing palmoplantar pustulosis. Furthermore, there was no difference in disease severity, onset age, or disease duration between patients with these heterozygous IL36RN variants and those without (p > 0.1). Study limitation: Lack of the further evaluation of IL36Ra protein in palmoplantar pustulosis lesions. Conclusions: The four variants of IL36RN identified did not appear to be associated with the specific phenotypes of palmoplantar pustulosis.

El polimorfismo rs12979860 C> T en el gen Interferón lambda 4 no está asociado a riesgo de fibrosis hepática en pacientes chilenos con hepatitis crónica por virus C / Interferon Lambda 4 RS12979860 C> T polymorphism is not associated with liver fibrosis in patients with hepatitis C

Background. Host genetic predispositions may be important determinants of liver fibrosis in patients with chronic hepatitis C (CHC). The association between Interferon-L 4 (IFNL4) rs12979860 C>T polymorphism and risk of liver fibrosis in CHC is contradictory. Aim: To evaluate the impact of IFNL4 rs12979860 polymorphism on the risk of fibrosis in patients with CHC. Material and Methods: One hundred fifty patients with CHC aged 50 ± 11 years (89 females) were genotyped for IFNL4 rs12979860 using real time PCR. Fibrosis present in liver biopsies was assessed using the METAVIR score, comparing patients with either no fibrosis, mild fibrosis, or intermediate fibrosis (F0+F1+F2, n = 96), with patients with severe fibrosis or cirrhosis (F3+F4, n = 54). Results: In F0-F2 patients the distribution of rs12979860 genotypes was 22 CC, 57 CT and 17 TT, whereas in patients F3-F4 the distribution was 10, 29 and 15, respectively. No association between IFNL4 rs12979860 genotype and risk of fibrosis was observed in uni or multivariate analyses. Conclusions: IFNL4 rs12979860 C>T polymorphism is not associated with risk of liver fibrosis in this group of patients with CHC.

Profile of HIV subtypes in HIV/HBV- and HIV/HCV-coinfected patients in Southern Brazil

Abstract INTRODUCTION: HIV and viral hepatitis infections are major causes of chronic disease worldwide and have some similarities with regard to routes of transmission, epidemiology, front barriers faced during access of treatment, and strategies for a global public health response. The objective was to describe the HIV-1 subtypes, viral tropism and single-nucleotide polymorphisms (SNPs) of interleukin 28B (IL28B) from a case series of HIV/viral hepatitis coinfected patients from southern Brazil. METHODS: Clinical and epidemiological data were evaluated by a review of medical records. Periodic blood draws were taken to determine the viral and host characteristics. RESULTS: This study included 38 patients with HIV/HBV or HIV/HCV coinfection; the median age was 49 years. Thirty-seven (97.4%) were on antiretroviral therapy, 32 (84.2%) had an undetectable viral load, a median CD4+ T-cell count of 452 cells/mm3. HIV-1 subtyping showed 47.4 and 31.6% of patients with subtypes C and B, respectively. Analysis of viral co-receptor usage showed a predominance of the R5 variant (64.7%), with no significant difference between the subtypes. Twenty patients with HIV/HCV coinfection were eligible to receive HCV therapy with pegylated-interferon-alpha plus ribavirin, and 10/20 (50%) of them achieved sustained virological response. SNPs of IL28B were evaluated in 93.3% of patients with HIV/HCV coinfection, and 17 (60.7%) presented the CC genotype. CONCLUSIONS: In the present case series, a higher frequency of HIV subtype C was found in coinfected patients. However such findings need to be prospectively evaluated with the inclusion of data from regional multicenter analyses.

Association between interleukin-22 genetic polymorphisms and bladder cancer risk

OBJECTIVE:The cytokine interleukin-22 (IL-22), which is produced by T cells and natural killer cells, is associated with tumorigenesis and tumor progression in cancers. However, the role of IL-22 in bladder cancer has not been investigated.MATERIALS AND METHODS:A prospective hospital-based case-control study comprising 210 patients with pathologically proven bladder cancer and 210 age- and gender-matched healthy controls was conducted. The genotypes of 3 common polymorphisms (-429 C/T, +1046 T/A and +1995 A/C) of the IL-22 gene were determined with fluorogenic 5' exonuclease assays.RESULTS:Patients with bladder cancer had a significantly higher frequency of the IL-22 -429 TT genotype [odds ratio (OR)=2.04, 95% confidence interval (CI)=1.19, 3.49; p=0.009] and -429 T allele (OR=1.42, 95% CI=1.08, 1.87; p=0.01) than the healthy controls. These findings were still significant after a Bonferroni correction. When stratifying according to the stage of bladder cancer, we found that patients with superficial bladder cancer had a significantly lower frequency of the IL-22 -429 TT genotype (OR=0.48, 95% CI=0.23, 0.98; p=0.04). When stratifying according to the grade and histological type of bladder cancer, we found no statistical association. The IL-22 +1046 T/A and IL-22 +1995 A/C gene polymorphisms were not associated with the risk of bladder cancer.CONCLUSION:To the authors' knowledge, this is the first report documenting that the IL-22 -429 C/T gene polymorphism is associated with bladder cancer risk. Additional studies are required to confirm this finding.

Análisis molecular del cáncer de colon esporádico / Molecular analysis of sporadic colon cancer

Background: In Chile, colorectal cancer (CRC) is often diagnosed in late stages. Thus, surgical treatment must be complemented with chemotherapy. KRAS mutations and microsatellite instability have been detected in these tumors. However, the response to treatment in patients without KRAS mutations varies and requires a better understanding. Aim: To determine the frequency and distribution of somatic point mutations in KRAS, BRAF and PIK3CA genes and microsatellite instability status (MSI) in patients with colon cancer (CC). Material and Methods: A prospective observational study of patients undergoing surgery for colon cancer. Tumor-derived DNA was analyzed by polymerase chain reaction (PCR) for the most frequent mutations of KRAS, BRAF and PIK3CA. PCR was also used to analyze MSI. Results: Fifty-eight patients with sporadic CC were analyzed, 16 showed KRAS mutations (G12R, G12D, G12V, G13D) and out of the 42 patients that did not show any mutation, 10 had mutations in BRAF (V600E) and PIK3CA (E542K, E545D, E545K, Q546E, H1047R). BRAF mutations alone or in combination with PIK3CA mutations were observed in 27% of high MSI tumors and in 2% of tumors without instability (p < 0.049). A higher percentage of high MSI tumors were located in the right colon (p < 0.001), and showed BRAF mutation (p < 0.020). Conclusions: The highest percentage of high MSI and BRAF mutations was observed in the right colon. Therefore, this study suggests the presence of different molecular features between right and left colon tumors that should be considered when defining the therapeutic management.

A 2015 roadmap for the management of hepatitis C virus infections in Asia

The prevalence of hepatitis C virus (HCV) in Asia is 0.5% to 4.7%, with three different genotypes predominating, depending on the geographic region: genotype 1b in East Asia, genotype 3 in South and Southeast Asia, and genotype 6 in Indochina. Official approval for direct-acting antiviral agents (DAAs) in Asia lags significantly behind that in the West, such that in most countries the mainstay of therapy is still pegylated interferon and ribavirin (PR). Because the interleukin-28B genetic variant, associated with a high sustained virologic response (SVR), is common in Asians, this treatment is still acceptable in Asian patients with HCV infections. A roadmap for HCV therapy that starts with PR and takes into account those DAAs already approved in some Asian countries can provide guidance as to the best strategies for management, particularly of genotype 1 and 3 infections, based on SVR rates. Sofosbuvir and PR are likely to be the initial therapies for genotype 1 and 3 disease, although in the former these drugs may be suboptimal in patients with cirrhosis (62% SVR) and the extension of treatment to 24 weeks may be required. For difficult to treat genotype 3 infections in treatment-experienced patients with cirrhosis, a combination of sofosbuvir and PR result in an 83% SVR and is, therefore, currently the optimal treatment regimen. Treatment failure is best avoided since data on rescue therapies for DAA failure are still incomplete.

Effects of bromopride on expression of metalloproteinases and interleukins in left colonic anastomoses: an experimental study

Anastomotic dehiscence is the most severe complication of colorectal surgery. Metalloproteinases (MMPs) and interleukins (ILs) can be used to analyze the healing process of anastomosis. To evaluate the effects of bromopride on MMP and cytokine gene expression in left colonic anastomoses in rats with or without induced abdominal sepsis, 80 rats were divided into two groups for euthanasia on the third or seventh postoperative day (POD). They were then divided into subgroups of 20 rats for sepsis induction or not, and then into subgroups of 10 rats for administration of bromopride or saline. Left colonic anastomosis was performed and abdominal sepsis was induced by cecal ligation and puncture. A colonic segment containing the anastomosis was removed for analysis of gene expression of MMP-1α, MMP-8, MMP-13, IL-β, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). On the third POD, bromopride was associated with increased MMP-1α, MMP-13, IL-6, IFN-γ, and IL-10 gene expression. On the seventh POD, all MMP transcripts became negatively modulated and all IL transcripts became positively modulated. In the presence of sepsis, bromopride administration increased MMP-8 and IFN-γ gene expression and decreased MMP-1, TNF-α, IL-6, and IL-10 gene expression on the third POD. On the seventh POD, we observed increased expression of MMP-13 and all cytokines, except for TNF-α. In conclusion, bromopride interferes with MMP and IL gene expression during anastomotic healing. Further studies are needed to correlate these changes with the healing process.

No association between the IL28B SNP and response to peginterferon plus ribavirin combination treatment in Korean chronic hepatitis C patients

BACKGROUND/AIMS: There are few available data regarding the association between the single nucleotide polymorphisms (SNPs) of the gene encoding interleukin 28B (IL28B) and a sustained virologic response (SVR) to peginterferon (PEG-IFN) plus ribavirin (RBV) therapy in Korean chronic hepatitis C patients. METHODS: This was a retrospective cohort study of 156 patients with chronic hepatitis C virus (HCV) infection who received combination treatment of PEG-IFN plus RBV. Blood samples from these patients were analyzed to identify the IL28B SNPs at rs12979860, rs12980275, rs8099917, and rs8103142. Association analyses were performed to evaluate the relationships between each IL28B SNP and SVRs. RESULTS: Seventy six patients with HCV genotype 1 and 80 with genotype non-1 were enrolled. The frequencies of rs12979860 CC and CT genotypes were 90.4% and 9.6%, respectively; those of rs12980275 AA and AG genotypes were 87.2% and 12.8%, respectively; those of rs8099917 TT and TG genotypes were 92.3% and 7.7%, respectively; and those of rs8103142 TT and CT genotypes were 90.4% and 9.6%, respectively. Among the patients with HCV genotype 1, the SVR rates were 69.7% and 80.0% for rs12979860 CC and CT, respectively (P=0.71). Among the HCV genotype non-1 patients, SVR rates were 88.0% and 100% for rs12979860 CC and CT (P=1.00), respectively. CONCLUSIONS: Genotypes of the IL28B SNP that are known to be favorable were present in most of the Korean patients with chronic hepatitis C in this study. Moreover, the IL28B SNP did not influence the SVR rate in either the HCV genotype 1 or non-1 patients. Therefore, IL28B SNP analysis might be not useful for the initial assessment, prediction of treatment outcomes, or treatment decision-making of Korean chronic hepatitis C patients.

Role of Interleukin-28B Genetic Polymorphisms in Korean Patients with Hepatitis C Virus Infection

BACKGROUND/AIMS: This study investigated the role of single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B) gene with respect to clinical outcomes and the antiviral response in hepatitis C virus (HCV) infection to suggest the practical utility of IL28B genotyping in Korea. METHODS: Two SNPs near IL28B, rs12979860 and rs8099917, were analyzed using an allelic discrimination assay in a total of 454 individuals, including 147 health-check examinees and 307 patients with HCV infection. RESULTS: The CC genotype frequency was significantly higher in the spontaneous recovery group than in the chronic infection group and was higher in the chronic hepatitis group than in the liver cirrhosis or hepatocellular carcinoma group, suggesting its favorable role in the clinical outcome. Multivariate analysis revealed that the rs12979860 CC genotype was an independent predictor of sustained virologic response (SVR) in genotype 1 HCV infection. During the currently used response-guided therapy, IL28B genotyping was most helpful for the patients who exhibit early virologic responses without rapid virologic responses, as those patients exhibiting the non-CC type did not achieve SVR, although they represented approximately one-third of the total patients. CONCLUSIONS: The IL28B SNP is an independent predictor of SVR. Our results may be helpful if the findings are carefully applied to select patients in Korea.

Myxovirus resistance, osteopontin and suppressor of cytokine signaling 3 polymorphisms predict hepatitis C virus therapy response in an admixed patient population: comparison with IL28B

OBJECTIVES: Suppressor of cytokine signaling 3, myxovirus resistance protein and osteopontin gene polymorphisms may influence the therapeutic response in patients with chronic hepatitis C, and an association with IL28 might increase the power to predict sustained virologic response. Our aims were to evaluate the association between myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 gene polymorphisms in combination with IL28B and to assess the therapy response in hepatitis C patients treated with pegylated-interferon plus ribavirin. METHOD: Myxovirus resistance protein, osteopontin, suppressor of cytokine signaling 3 and IL28B polymorphisms were analyzed by PCR-restriction fragment length polymorphism, direct sequencing and real-time PCR. Ancestry was determined using genetic markers. RESULTS: We analyzed 181 individuals, including 52 who were sustained virologic responders. The protective genotype frequencies among the sustained virologic response group were as follows: the G/G suppressor of cytokine signaling 3 (rs4969170) (62.2%); T/T osteopontin (rs2853744) (60%); T/T osteopontin (rs11730582) (64.3%); and the G/T myxovirus resistance protein (rs2071430) genotype (54%). The patients who had ≥3 of the protective genotypes from the myxovirus resistance protein, the suppressor of cytokine signaling 3 and osteopontin had a greater than 90% probability of achieving a sustained response (p<0.0001). The C/C IL28B genotype was present in 58.8% of the subjects in this group. The sustained virological response rates increased to 85.7% and 91.7% by analyzing C/C IL28B with the T/T osteopontin genotype at rs11730582 and the G/G suppressor of cytokine signaling 3 genotype, respectively. Genetic ancestry analysis revealed an admixed population. CONCLUSION: Hepatitis C genotype 1 patients who were responders to interferon-based therapy had a high frequency of multiple protective polymorphisms in the myxovirus ...

Response to treatment in Brazilian patients with chronic hepatitis C is associated with a single-nucleotide polymorphism near the interleukin-28B gene

A single-nucleotide polymorphism (SNP) upstream of interleukin (IL)28B was recently identified as an important predictor of the outcome of chronic hepatitis C patients treated with pegylated interferon plus ribavirin (PEG-IFN/RBV). The aim of this study was to investigate the association between the IL28B gene polymorphism (rs12979860) and virological response in chronic hepatitis C patients. Brazilian patients (n = 263) who were infected with hepatitis C virus (HCV) genotype 1 and were receiving PEG-IFN/RBV were genotyped. Early virological response (EVR) (12 weeks), end-of-treatment response (EOTR) (48 weeks), sustained virological response (SVR) (72 weeks) and relapse were evaluated using conventional and quantitative polymerase chain reaction (PCR) assays. The frequency of the C allele in the population was 39%. Overall, 43% of patients experienced SVR. The IL28B CC genotype was significantly associated with higher treatment response rates and a lower relapse rate compared to the other genotypes [84% vs. 58% EVR, 92% vs. 63% EOTR, 76% vs. 38% SVR and 17% vs. 40% relapse rate in CC vs. other genotypes (CT and TT), respectively]. Thus, the IL28B genotype appears to be a strong predictor of SVR following PEG-IFN/RBV therapy in treatment-naïve Brazilian patients infected with HCV genotype 1. This study, together with similar research examining other SNPs, should help to define adequate protocols for the treatment of patients infected with HCV genotype 1, especially those with a poor prognosis.

The Impact of Inosine Triphosphatase Variants on Hemoglobin Level and Sustained Virologic Response of Chronic Hepatitis C in Korean

Two variants of the inosine triphosphatase (ITPA: rs1127354, rs7270101) gene cause ITPA deficiency and protect against the hemolytic toxicity of ribavirin. We investigated the clinical significance of ITPA variants in Korean patients treated with pegylated interferon (PEG-IFN) plus ribavirin. Of the 133 patients, 108 were CC and 25 were non-CC at rs1127354 (groups A and B, respectively). On the other hand, at rs7270101 all 133 were AA. The mean values of Hemoglobin (Hgb) after 4, 8, and 12 weeks of treatment in groups A and B were 12.2 and 14.0, 11.8 and 13.2, and 11.5 and 12.9, respectively (P=0.001, 0.036, 0.036). Sustained virologic response (SVR) was achieved in 67.8% (40/59) of genotype 1 patients and in 75% (27/36) of non-genotype 1 patients. Regarding ITPA variants, SVR was achieved by 66% and 80% of genotype 1 (P=0.282), and by 78% and 71% (P=0.726) of non-genotype 1. SVR was not significantly different in groups A and B. In conclusion, non-CC at rs1127354 without involvement of rs7270101 is strongly associated with protection from ribavirin-induced anemia, however, ITPA genotype is not associated with SVR.

Inhibitory Effect of Melanoma Differentiation Associated Gene-7/Interleukin-24 on Invasion In Vitro of Human Melanoma Cancer Cells

The acquisition of metastasis potential is a critical point for malignant tumors. Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) is a potential tumor suppress gene and frequently down-regulated in malignant tumors. It has been implicated that overexpression of MDA-7 led to proliferation inhibition in many types of human tumor. Invasion is an important process which is potential to promote tumor metastasis. However, the role and potential molecular mechanism of mda-7/IL-24 to inhibit the invasion of human melanoma cancer is not fully clear. In this report, we identified a solid role for mda-7/IL-24 in invasion inhibition of human melanoma cancer LiBr cells, including decreasing of adhesion and invasion in vitro, blocking cell cycle, down-regulating the expression of ICAM-1, MMP-2/9, CDK1, the phosphorylation of ERK and Akt, NF-kappaB and AP-1 transcription activity. Meanwhile, there was an increased expression of PTEN in mda-7/IL-24 over-expression LiBr cells. Our results demonstrated that mda-7/IL-24 is a potential invasion suppress gene, which inhibits the invasion of LiBr cells by the down-regulation of ICAM-1, MMP-2/9, PTEN, and CDK1 expression. The molecular pathways involved were the MAPK/ERK, PI3K-Akt, NF-kappaB, and AP-1. These findings suggest that mda-7/IL-24 may be used as a possible therapeutic strategy for human melanoma cancer.

Impact of Interleukin-28B gene polymorphism [rs12979860] on Egyptian patients infected with hepatitis C virus genotype-4

Single nucleotide polymorphisms [SNPs] in the Interleukin [IL]-28B gene, namely rs12979860, could predict response to pegylated interferon-alpha-ribavirin [PR] therapy in hepatitis C virus genotype 1 [HCV-1]-infected patients. A similar role was investigated in a case-control study conducted on 93 Egyptian patients chronically infected with HCV-4 in comparison to 22 individuals with spontaneous HCV clearance and 70 healthy volunteers. The homozygous C allele genotype [CC] was associated with sustained viral response [SVR] to therapy compared with the homozygous T allele genotype [TT] and the heterozygous genotype [CT]. In the SVR group, the response rate was statistically significantly higher in CC genotypes [58.6%] compared with CT/TT [20.3%]. There was no correlation between SVR patients' genotypes and early response to therapy or HCV baseline viral load. Our findings describe how IL-28B SNP genotyping may guide appropriate selection of HCV-4-infected patients for PR therapy. We underscore IL28B genotyping as a tool that might increase PR cost-benefit in Egypt

Heterologous expression of human IL-29 [IFN-lamda1] in Iranian lizard leishmania

Interferons with different functions such as antiviral, antiproliferative and immunomodulatory actions are effective medications for a number of diseases. One of these new interferons [IFNs] is Interleukin-29 [IL-29] belongs to the family of IFN-lamda has antiviral activity and its potent in accompanying with IFN-alpha in treatment of HCV infection has been evaluated [clinical trial phase II]. Recombinant IL-29 has been previously produced in multiple expression systems but in this study we cloned and expressed this protein in an Iranian Lizard leishmania [I.L.L] for the first time. The Main objective of this research was to evaluate expression of functional human IL-29 in domestic Lizard leishmania as an alternative eukaryotic expression system. The IL-29 expression cassette was constructed into a pLEXSY vector. The leishmania cells were transfected by electroporation. After selection of transfectants, the protein expression was evaluated at RNA and protein levels. Expression cassette was successfully transfected to leishmania cells and expression of recombinant IL-29 was proved by RT-PCR and western blotting. Purified protein showed 20% activity compared to standard protein. Enzymatic removal of N-glycan resulted to the shift of protein mobility on SDS-PAGE. Easy handling and culture of this eukaryotic host and mammalian cell like posttranslational modifications are the main advantages of this expression host, but the expression yield of this protein is very low and it seems to be not economic for large-scale production.

A single nucleotide polymorphism, rs129679860, in the IL28B locus is associated with the viral kinetics and a sustained virological response in a chronic, monoinfected hepatitis C virus genotype-1 Brazilian population treated with pegylated interferon-ribavirin

Single nucleotide polymorphisms (SNPs) in the interleukin (IL)28B locus have been associated with a sustained virological response (SVR) in interferon-ribavirin (IFN-RBV)-treated chronic hepatitis C virus (HCV)-infected patients in European and African populations. In this study, the genotype frequency of two IL28B SNPs (rs129679860 and rs8099917) in a cohort of chronic HCV-monoinfected patients in Brazil was evaluated and the SNP sufficient to predict the treatment response outcome was determined. A total of 66 naïve genotype-1 chronic HCV-infected patients were genotyped and the associated viral kinetics and SVR were assessed. The overall SVR was 38%. Both the viral kinetics and SVR were associated with rs129679860 genotypes (CC = 62% vs. CT = 33% vs. TT = 18%, p = 0.016). However, rs8099917 genotypes were only associated with SVR (TT = 53% vs. TG = 33% vs. GG = 18%; p = 0.032). In this population, the analysis of a single SNP, rs12979860, successfully predicts SVR in the IFN-RBV treatment of HCV.

Efficacy of peginterferon and ribavirin is associated with the IL28B gene in Korean patients with chronic hepatitis C

BACKGROUND/AIMS: Sustained virologic response (SVR) for the treatment of chronic hepatitis C (CHC) may differ with ethnicity due to differences in genetic traits. This study evaluated the efficacy of peginterferon and ribavirin, and the association between IL28B genotypes and the treatment efficacy in Korean CHC patients. METHODS: This was a retrospective cohort study using data from medical records. Eighty-five CHC patients were eligible for assessment of the efficacy of antiviral therapy, and 47 patients were available for an IL28B genetic study, which was performed using the Multiplex tetra-primer PCR method for rs12979860. RESULTS: Overall, the early virologic response rate was 87.1%: 84.9% in HCV genotype 1 and 90.6% in genotype 2. The overall end-of-treatment virologic response rate was 81.2%: 75.5% in genotype 1 and 90.6% in genotype 2. The overall SVR rate was 81.2%: 75.5% in genotype 1 and 90.6% in genotype 2. For rs12979860, the frequencies of polymorphisms were 89% for the CC type, 11% for the CT type, and 0% for the TT type. Their overall SVR rate was 87% (39/47): 90.5% (38/42) for the CC type and 20% (1/5) for the CT type. For genotype 1, SVR rates were 88% (21/24) for the CC type and 0% (0/4) for the CT type. Multivariate analysis revealed that the IL28B-CC type was a good predictor for SVR. CONCLUSIONS: The SVR of the combination therapy in Koreans was higher than that observed in Western countries. This finding might be attributable to the high prevalence of IL28B-CC type among Koreans, which may be a good predictor of SVR.

Enfermedad inflamatoria intestinal: Una mirada inmunológica: [revisión] / Inflammatory bowel diseases: An immunological approach: [review]

Inflammatory bowel diseases (IBD) are inflammatory diseases with a multifactorial component that involve the intestinal tract. The two relevant IBD syndromes are Crohn's disease (CD) and ulcerative colitis (UC). One factor involved in IBD development is a genetic predisposition, associated to NOD2/CARD15 and Toll-like receptor 4 (TLR4) polymorphisms that might favor infectious enterocolitis that is possibly associated to the development of IBD. The identification of specific immunologic alterations in IBD and their relationship to the etiology of the disease is a relevant research topic. The role of intra and extracellular molecules, such as transcription factors and cytokines that are involved in the inflammatory response, needs to be understood. The relevance of immunologic molecules that might drive the immune response to a T helper (Th) 1, Th 2 or the recently described Th 17 phenotype, has been demonstrated in animal models and clinical studies with IBD patients. CD and UC predominantly behave with a Th 1 and Th 2 immune phenotype, respectively. Recently, an association between CD and Th 17 has been reported. The knowledge acquired from immunologic and molecular research will help to develop accurate diagnostic methods and efficient therapies.