Department of Nephrology, Transplantology and Internal Diseases, Poznań University of Medical Sciences, 49 Przybyszewskiego Blvd, 60-355 Poznań, Poland.
BMC Nephrol. 2012 Aug 3;13:75. doi: 10.1186/1471-2369-13-75.
The interleukin (IL)18 rs360719 CC genotype is associated with the development of antibodies to hepatitis B virus surface antigen (anti-HBs) in hemodialysis (HD) patients. IL18 shares biological properties with IL12 in promoting the T-hepler 1 (Th1) system. We studied whether polymorphisms in the IL12A 3 untranslated region (UTR) and IL12B 3UTR may contribute to anti-HBs development (titre ≥ 10 IU/L) in HD patients either individually or jointly with the IL18 polymorphism.
In 518 HD patients and 240 controls the IL12A rs568408 3'UTR G > A polymorphism was genotyped by high-resolution melting curve analysis. Polymerase chain reaction restriction fragment length polymorphism was used to detect the IL12B rs3212227 3'UTR A > C and IL18 -1297 T > C rs360719 polymorphisms. The associations between the IL12A, IL12B and IL18 genotypes and the risk of impaired anti-HBs development were estimated by computing the odds ratios and their 95% confidence intervals using logistic regression analysis.
In the logistic regression analysis, the higher frequency of rs360719 CC individually (2.9% in 207 patients without anti-HBs development vs 8.0% in 311 patients with anti-HBs development, p = 0.009) and of rs360719 CC combined with rs568408 GG (p = 0.048), rs568408 GA (p = 0.035), rs568408 GG/AA (p = 0.034) or rs3212227 AA (p = 0.046) was associated with an increased chance for the development of anti-HBs in HD patients. Patients bearing both rs568408 AA and rs360719 TT had a 10.9-fold or 8.9-fold lower chance, respectively, to develop anti-HBs compared with those carrying any other genotype (p = 0.005) or those who had both wild-type rs568408 GG and rs360719 TT (p = 0.011). Carriers of both rs3212227 CC and rs360719 TC had a 4.6-fold lower chance for anti-HBs development than carriers of any other genotype (p = 0.042).
Development of anti-HBs in HD patients is associated with gene polymorphisms of interleukins involved in the Th1 system.
白细胞介素（IL）18 rs360719 CC 基因型与血液透析（HD）患者乙型肝炎表面抗原（抗-HBs）抗体的发展有关。IL18 在促进 T 辅助 1（Th1）系统方面与 IL12 具有生物学特性。我们研究了白细胞介素 12A 3非翻译区（UTR）和白细胞介素 12B 3UTR 中的多态性是否单独或与 IL18 多态性一起导致 HD 患者抗-HBs 的发展（滴度≥10 IU/L）。
在 518 名 HD 患者和 240 名对照中，通过高分辨率熔解曲线分析对 IL12A rs568408 3'UTR G > A 多态性进行基因分型。聚合酶链反应限制片段长度多态性用于检测 IL12B rs3212227 3'UTR A > C 和 IL18 -1297 T > C rs360719 多态性。通过计算逻辑回归分析的优势比及其 95%置信区间，估计 IL12A、IL12B 和 IL18 基因型与受损抗-HBs 发展风险之间的关联。
在逻辑回归分析中，rs360719 CC 的频率较高（207 名无抗-HBs 发展的患者中为 2.9%，311 名有抗-HBs 发展的患者中为 8.0%，p=0.009），rs360719 CC 与 rs568408 GG（p=0.048）、rs568408 GA（p=0.035）、rs568408 GG/AA（p=0.034）或 rs3212227 AA（p=0.046）的组合与 HD 患者抗-HBs 的发展机会增加相关。与携带任何其他基因型（p=0.005）或携带野生型 rs568408 GG 和 rs360719 TT（p=0.011）的患者相比，同时携带 rs568408 AA 和 rs360719 TT 的患者发生抗-HBs 的几率分别降低了 10.9 倍或 8.9 倍。与携带任何其他基因型的患者相比，同时携带 rs3212227 CC 和 rs360719 TC 的患者发生抗-HBs 的几率降低了 4.6 倍（p=0.042）。
HD 患者抗-HBs 的发展与 Th1 系统中涉及的白细胞介素的基因多态性有关。
