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

• Published in: BMC nephrology Vol. 18; no. 1; pp. 165 - 7
• Main Authors: Grzegorzewska, Alicja E., Świderska, Monika K., Mostowska, Adrianna, Warchoł, Wojciech, Jagodziński, Paweł P.
• Format: Journal Article
• Language: English
• Published: London BioMed Central 19.05.2017; BMC
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Alleles; Antigens; Cytokines; Cytokines - genetics; Female; Gene expression; Genes; Genetic Association Studies; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Genetics; Genotyping; Helper cells; Hemodialysis; Hepatitis; Heredity; Homozygotes; Humans; Immunoglobulins; Incidence; Infections; Inflammation; Interferon; Interferon λ3; Interferons; Interleukin 1; Interleukin 13; Interleukin 18; Interleukin 4 receptors; Interleukin-1 - immunology; Interleukin-12 Subunit p35 - genetics; Interleukins - genetics; Internal Medicine; Kidney Failure, Chronic - genetics; Kidney Failure, Chronic - mortality; Kidney Failure, Chronic - therapy; Lymphocytes T; Male; Medicine; Medicine & Public Health; Middle Aged; Monocyte chemoattractant protein 1; Mortality; Nephrology; Poland - epidemiology; Polymerase chain reaction; Polymorphism, Single Nucleotide - genetics; Population; Renal Dialysis - mortality; Renal Dialysis - statistics & numerical data; Reproducibility of Results; Research Article; Restriction fragment length polymorphism; Risk Factors; Sensitivity and Specificity; Software; Survival; Survival Rate; T helper cells; Tumors; Young Adult; Poland; Interferon λ3; T helper cells; Cytokines; Hemodialysis; Survival; Genes
• ISSN: 1471-2369; 1471-2369
• DOI: 10.1186/s12882-017-0582-x

Background Circulating 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. Methods The 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. Results In 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. Conclusions Polymorphisms of IFNL3 rs8099917 and IL12A rs568408 contribute to survival of HD patients, but not as independent factors.