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Correlation of CCR5 and NLRP3 gene polymorphisms with renal damage due to hepatitis C virus-related cryoglobulinemia.

ABSTRACT: Correlation of C-C chemokine receptor type 5 (CCR5) and NACHT, LRR and PYD domain-containing protein 3 (NLRP3) gene polymorphisms with renal damage due to hepatitis C virus (HCV)-related cryoglobulinemia were investigated. The 1:1 matched case-control study design was adopted, 171 patients with renal damage due to HCV-related cryoglobulinemia were selected as the case group, and 171 patients without renal damage were selected as the control group. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis was used to detect the polymorphisms of locus rs1799987A/G in CCR5 gene and locus rs35829419A/C in NLRP3 gene of 171 pairs of HCV patients. SPSS 20.0 software was used for logistic regression analysis, and genetics package of the R programming language for Hardy-Weinberg equilibrium test. The frequencies of locus rs1799987A/G in CCR5 gene in the case group were 48.0 and 52.0%, while those in the control group were 47.9 and 52.1%; the frequencies of locus rs35829419A/C in NLRP3 gene were 55.8 and 44.2%, while those in the control group were 55.3 and 44.7%. The results of logistic regression analysis showed that the distribution of CCR5 gene polymorphism in the case group was statistically different from that in the control group (P<0.05), which had a statistical correlation with the renal damage due to HCV-related cryoglobulinemia (P<0.05). At rs1799987, GG genotype was compared with AA genotype, and AG genotype was compared with AA genotype; the results showed that the renal damage due to HCV-related cryoglobulinemia was not decreased [odds ratio (OR) = 0.91, 95% confidence interval (95% CI): 0.47-1.54; OR = 0.89, 95% CI: 0.49-1.31]. The negative analysis model of the GG genotype reduced the risk of renal damage due to HCV-related cryoglobulinemia remarkably (OR = 0.62, 95% CI: 0.39-0.98). Rs1799987A/G and gene polymorphism of CCR5 may be associated with renal damage due to HCV-related cryoglobulinemia, and the carriage of G allele may lower the incidence rate of the disease, while rs35829419A/C in NLRP3 has no correlation with renal damage due to HCV-related cryoglobulinemia.

SUBMITTER: Wang M

PROVIDER: S-EPMC6125838 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Correlation of CCR5 and NLRP3 gene polymorphisms with renal damage due to hepatitis C virus-related cryoglobulinemia.

Wang Mengjun M Liu Qiuli Q Liu Chunhua C

Experimental and therapeutic medicine 20180801 4

Correlation of C-C chemokine receptor type 5 (CCR5) and NACHT, LRR and PYD domain-containing protein 3 (NLRP3) gene polymorphisms with renal damage due to hepatitis C virus (HCV)-related cryoglobulinemia were investigated. The 1:1 matched case-control study design was adopted, 171 patients with renal damage due to HCV-related cryoglobulinemia were selected as the case group, and 171 patients without renal damage were selected as the control group. Polymerase chain reaction and restriction fragme ...[more]

PMID: 30214525

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Project description:UnlabelledHepatitis C virus (HCV) is the most common cause of mixed cryoglobulinemia syndrome (MCS). The efficacy and safety of all-oral direct-acting antiviral (DAA) therapy in HCV-associated MCS (HCV-MCS) is largely unknown. The authors studied case series of patients with HCV-MCS who were treated with sofosbuvir-based regimens and historical controls treated with pegylated interferon and ribavirin in a single health care network. HCV-MCS was defined by circulating cryoglobulin associated with systemic vasculitis symptoms. Renal involvement (n = 7) was established by kidney biopsy (n = 5) or by two or more of the following clinical findings: reduced kidney function, proteinuria, or hematuria with other causes excluded (n = 2). Twelve patients received DAA therapy between December 2013 and September 2014. Median age was 61 years, 58% were male, and 50% had cirrhosis. Median baseline serum creatinine was 0.97 mg/dL (range 0.7-2.47). Four patients received rituximab concurrent with DAA therapy. Sustained virological response rate at 12 weeks (SVR12) was 83% overall. Patients with glomerulonephritis who achieved SVR12 experienced an improvement in serum creatinine and a reduction in proteinuria. Cryoglobulin levels decreased in 89% of patients, with median percent decreasing from 1.5% to 0.5% and completely disappearing in four of nine cases who had cryoglobulins measured after treatment. Serious adverse events were infrequent (17%). In contrast, the historical cohort treated with pegylated interferon and ribavirin experienced only 10% SVR12, with 100% experiencing at least one adverse event and 50% experiencing premature discontinuation due to adverse events.ConclusionSVR12 rates for sofosbuvir-based DAA regimens in HCV-MCS were 83%, significantly higher than historical controls treated with pegylated interferon and ribavirin; patients with glomerulonephritis experienced improvement in renal function, including those not concomitantly treated with immunosuppression.

Project description:BACKGROUND:Cytokines are proteins that mediate innate and adaptive immunity responses. It is hypothesized that interferon lambda 3 (IFNL3) levels can influence the outcome of chronic hepatitis B virus (HBV) infection. Polymorphisms in IFN genes have been associated with response to infection. OBJECTIVES:This study was carried-out to investigate the association of IFNL3 gene polymorphisms (rs12979860 and rs8099917) with HBV susceptibility, in chronic HBV-infected patients. PATIENTS AND METHODS:In this case-control study, we determined IFNL3 single nucleotide polymorphisms (SNPs) (rs12979860 and rs8099917) in 221 individuals, with chronic HBV infection, and 200 healthy individuals, who were voluntary blood donors, with negative test for HBV. Alleles and genotypes analyses were performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. RESULTS:The frequencies of the rs12979860 and rs8099917 genotypes were not significantly different between the HBV-infected and the control groups (CC:CT:TT of 30.3%:48.0%:21.7% vs. 33.0%:49.0%:18.0%, P > 0.05, and GG:GT:TT of 5.8%:39.4%:54.8% vs. 5.0%:41.0%:54.0%, P > 0.05, respectively). Also, the frequencies of the alleles were not significantly different between both groups (C:T of 54.3%:45.7% vs. 57.5%:42.5%, P > 0.05, and G:T of 25.6%:74.4% vs. 25.5%:74.5%, P > 0.05, respectively) and the chronic HBV infection. There were no significant differences between patients, with at least one rs12979860C and or rs8099917T alleles compared to the healthy controls (rs12979860: CT + CC:TT, OR = 1.26, 95%CI = 0.78 - 2.04, P = 0.341 and rs8099917: GT + TT:GG, OR = 1.03, 95%CI = 0.70 - 1.51, P = 0.877, respectively). CONCLUSIONS:Our study showed no correlation between rs12979860 and rs8099917 SNPs and chronic HBV infection. Further studies, with larger sample sizes and different ethnicities, are necessary to validate our findings.

Dataset Information

Correlation of CCR5 and NLRP3 gene polymorphisms with renal damage due to hepatitis C virus-related cryoglobulinemia.

Publications

Correlation of CCR5 and NLRP3 gene polymorphisms with renal damage due to hepatitis C virus-related cryoglobulinemia.

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