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Abstract：
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.
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.
摘要：
背景：循环促炎细胞因子与相对死亡风险增加相关，而反映T细胞功能改善的免疫参数是血液透析（HD）患者生存的预测因子。我们在前瞻性研究中评估了T辅助细胞细胞因子相关基因的变异是否是HD患者死亡率的决定因素。
方法：这项研究是在532名流行HD受试者中进行的，他们随访了7年。HRM分析用于IFNL3、IL12A、IL13和IL4R基因分型。CCL2,IL12B,使用PCR-RFLP分析对IL18进行基因分型。使用Kaplan-Meier方法和Cox比例风险模型进行生存分析。
结果：在单变量分析中，在隐性遗传模型中,IFNL3rs8099917与全因死亡率相关(对数秩检验P=0.044),IL12Ars568408-在显性模型中(对数秩检验P=0.029)。IFNL3rs8099917中的次要纯合子（基因型GG）在研究期间显示出较短的生存期（3.6、1.0-7.0年vs4.7、0.1-7.0年，P=0.009）比主要等位基因（T）携带者。rs8099917GG患者的死亡风险高于其余患者（GT+TT）（OR1.94，95CI1.11-3.40，P=0.020）。IL12Ars568408中的主要纯合性（基因型GG）与较小等位基因（AAAG）携带者的死亡率更高（HR1.31，95CI1.02-1.69，P=0.035）。在多变量分析中，然而,上述多态性不是生存的独立预测因子.
结论：IFNL3rs8099917和IL12Ars568408的多态性有助于HD患者的生存，但不是作为独立因素。
方法：这项研究是在532名流行HD受试者中进行的，他们随访了7年。HRM分析用于IFNL3、IL12A、IL13和IL4R基因分型。CCL2,IL12B,使用PCR-RFLP分析对IL18进行基因分型。使用Kaplan-Meier方法和Cox比例风险模型进行生存分析。
结果：在单变量分析中，在隐性遗传模型中,IFNL3rs8099917与全因死亡率相关(对数秩检验P=0.044),IL12Ars568408-在显性模型中(对数秩检验P=0.029)。IFNL3rs8099917中的次要纯合子（基因型GG）在研究期间显示出较短的生存期（3.6、1.0-7.0年vs4.7、0.1-7.0年，P=0.009）比主要等位基因（T）携带者。rs8099917GG患者的死亡风险高于其余患者（GT+TT）（OR1.94，95CI1.11-3.40，P=0.020）。IL12Ars568408中的主要纯合性（基因型GG）与较小等位基因（AAAG）携带者的死亡率更高（HR1.31，95CI1.02-1.69，P=0.035）。在多变量分析中，然而,上述多态性不是生存的独立预测因子.
结论：IFNL3rs8099917和IL12Ars568408的多态性有助于HD患者的生存，但不是作为独立因素。
