Polymorphisms of T helper cell cytokine-associated genes and survival of hemodialysis patients – a prospective study

Abstract

BackgroundCirculating pro-inflammatory cytokines were associated with increased relative mortality risk, while immune parameters reflecting improved T-cell function were predictors of survival in hemodialysis (HD) patients. We evaluated in the prospective study whether variants in T helper cell cytokine-associated genes are determinants of mortality in HD patients.MethodsThe study was carried out in 532 prevalent HD subjects who were followed-up for 7 years. HRM analysis was used for IFNL3, IL12A, IL13, and IL4R genotyping. CCL2, IL12B, and IL18 were genotyped using PCR–RFLP analysis. Survival analyses were conducted using the Kaplan-Meier method and the Cox proportional hazard model.ResultsIn univariate analyses, IFNL3 rs8099917 was associated with all-cause mortality in recessive model of inheritance (log-rank test P = 0.044), IL12A rs568408 - in dominant model (log-rank test P = 0.029). Minor homozygotes (the genotype GG) in IFNL3 rs8099917 showed shorter survival during the study (3.6, 1.0–7.0 years vs 4.7, 0.1–7.0 years, P = 0.009) than the major allele (T) bearers. The rs8099917 GG patients demonstrated higher risk of death than the remaining patients (GT + TT) (OR 1.94, 95%CI 1.11–3.40, P = 0.020). Major homozygosity (the genotype GG) in IL12A rs568408 was associated with higher mortality than that shown in bearers of the minor allele (AA + AG) (HR 1.31, 95%CI 1.02–1.69, P = 0.035). In multivariate analyses, however, the mentioned polymorphisms were not independent predictors of survival.ConclusionsPolymorphisms of IFNL3 rs8099917 and IL12A rs568408 contribute to survival of HD patients, but not as independent factors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-017-0582-x) contains supplementary material, which is available to authorized users.

Titers of antibodies to the surface antigen of hepatitis B virus after vaccination in relation to immunity-related gene variants. A prospective study among hemodialysis patients

“…Response to HBV vaccination was found to be a positive factor of survival among HD patients. 5 Moreover, carriers of at least one A allele of the IL12A rs568408 SNV were reported to have significantly lower all-cause mortality rates when compared with GG carriers, 38 and, according to our results, they had significantly higher peak anti-HBs titers. Also, there were fewer responders among GG carriers to HBV vaccination, 38 and in our study, the GG genotype was a negative correlate of the maximum anti-HBs concentrations.…”

“…5 Moreover, carriers of at least one A allele of the IL12A rs568408 SNV were reported to have significantly lower all-cause mortality rates when compared with GG carriers, 38 and, according to our results, they had significantly higher peak anti-HBs titers. Also, there were fewer responders among GG carriers to HBV vaccination, 38 and in our study, the GG genotype was a negative correlate of the maximum anti-HBs concentrations. Therefore, the association between the genotype of IL12A rs568408 and postvaccination anti-HBs concentrations might have clinical implications for the survival of HD patients.…”

Interferon-λ3 Gene Polymorphic Variants, rs4803217 and rs12980275, Responsiveness to HBV Vaccine and Outcome of HBV and HCV Exposure in Hemodialyzed Patients

“…The associations of tested IFNL3 SNPs with survival were not convincing in the examined HD patients. Neither all subjects nor subgroups categorized by HBV/HCV infection showed an influence of IFNL3 SNPs on the death rate, possibly due to a lack of association with plasma IFN-λ3 levels (20,21).…”

“…Plasma IFN-λ3 levels were positive predictors of survival in prevalent HD patients (20). The variant homozygosity (GG) of rs8099917 predicted a lower probability of survival in a prospective study of HD patients (21). The IFNL3 polymorphic variants were not analyzed concerning the survival of HD subjects.…”

Opportunities and Challenges for Genetic Studies of End-Stage Renal Disease in Canada

“…Evidence is limited to candidate gene association studies, which have significant issues with reproducibility and publication bias. Studies looked for SNP associations with hemodialysis outcomes including vascular access issues, 56 - 61 biochemical indices, 62 - 65 inflammation, 66 - 68 cardiovascular comorbidities 66 , 69 - 75 and mortality 76 - 79 and PD outcomes including peritoneal transport characteristics, 80 - 84 peritonitis risk, 85 - 87 or risk of encapsulating peritoneal sclerosis 88 ( Supplemental Table 1 ). Sample sizes were inadequate to confidently identify variants of reasonable effect sizes (average sample size of 246, range 67-777 patients).…”