血液透析患者乙型肝炎病毒表面抗原抗体和白细胞介素 12、18 基因多态性。
Antibodies to hepatitis B virus surface antigen and interleukin 12 and interleukin 18 gene polymorphisms in hemodialysis patients.
机构信息
Department of Nephrology, Transplantology and Internal Diseases, Poznań University of Medical Sciences, 49 Przybyszewskiego Blvd, 60-355 Poznań, Poland.
出版信息
BMC Nephrol. 2012 Aug 3;13:75. doi: 10.1186/1471-2369-13-75.
BACKGROUND
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.
METHODS
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.
RESULTS
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).
CONCLUSION
Development of anti-HBs in HD patients is associated with gene polymorphisms of interleukins involved in the Th1 system.
背景
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）。
方法
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。
结果
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）。
结论
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。
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