Xie Hai Yang, Wang Wei Lin, Yao Min Ya, Yu Song Feng, Feng Xiao Ning, Jin Jing, Jiang Zhi Jun, Wu Li Ming, Zheng Shu Sen
Department of Hepatobiliary Pancreatic Surgery, Key Laboratory of Multiple Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, China.
Arch Med Res. 2008 May;39(4):420-8. doi: 10.1016/j.arcmed.2008.01.003. Epub 2008 Mar 4.
Acute rejection (AR) and hepatitis B virus (HBV) recurrence after liver transplantation (LT) are the two major complications leading to chronic graft dysfunction. Genomic polymorphisms in interleukin (IL)-10, tumor necrosis factor (TNF)alpha and transforming growth factor (TGF)beta1 genes have been found to affect the susceptibility to certain diseases. However, the relationship between cytokine gene polymorphisms and risk of AR as well as HBV recurrence after LT in Han Chinese has not been reported. The objective of the present study was to investigate the association of polymorphisms within these cytokine genes with the risk of AR as well as HBV recurrence.
One hundred eighty six Chinese LT recipients in which 41 patients developed AR and 29 patients experienced HBV recurrence were enrolled; 151 age- and gender-matched healthy individuals were selected as controls. Single-nucleotide polymorphisms (SNPs) at loci of IL-10 -1082, -819, -592, and TNFalpha -308, -238, as well as TGFbeta1 -988, -800, -509, +869, and +915 were determined by using DNA sequencing and then confirmed by restriction fragment length polymorphism (PCR-RFLP). Analyses of linkage disequilibrium and haplotype frequency were performed using Haploview program.
The -819 and -592 polymorphisms in the IL-10 gene were in complete linkage (r(2) = 1). Another linkage was found at -509 and +869 in the TGFbeta1 gene (r(2) = 0.66). A significant difference was observed in the distribution of allelic frequencies at position -819 and -592 in the IL-10 gene between ARs and non-ARs (p = 0.036, OR = 1.134, 95% CI 0.999-1.287 and p = 0.036, OR = 1.134, 95% CI 0.999-1.287, respectively). After adjustment for a Bonferroni correction, there was no significant difference between the polymorphism and AR (p >0.05). Furthermore, the overall genotype distribution between HBV recurrence patients and non-HBV recurrence patients was also not significantly different (p >0.05).
Our study suggests that gene polymorphisms of IL10, TNFalpha, and TGFbeta1 do not have a major independent role in AR and HBV recurrence after LT and may not be risk factors of AR and HBV recurrence after LT in Chinese liver transplant recipients.
肝移植（LT）后急性排斥反应（AR）和乙型肝炎病毒（HBV）复发是导致慢性移植物功能障碍的两大主要并发症。已发现白细胞介素（IL）-10、肿瘤坏死因子（TNF）α和转化生长因子（TGF）β1基因的基因组多态性会影响对某些疾病的易感性。然而，汉族人群中细胞因子基因多态性与LT后AR风险以及HBV复发之间的关系尚未见报道。本研究的目的是调查这些细胞因子基因内的多态性与AR风险以及HBV复发的关联。
纳入186例中国LT受者，其中41例发生AR，29例发生HBV复发；选择151名年龄和性别匹配的健康个体作为对照。通过DNA测序确定IL-10 -1082、-819、-592位点以及TNFα -308、-238位点，以及TGFβ1 -988、-800、-509、+869和+915位点的单核苷酸多态性（SNP），然后通过限制性片段长度多态性（PCR-RFLP）进行确认。使用Haploview程序进行连锁不平衡和单倍型频率分析。
IL-10基因中的-819和-592多态性处于完全连锁状态（r² = 1）。在TGFβ1基因的-509和+869位点发现另一个连锁（r² = 0.66）。AR患者和非AR患者之间，IL-10基因-819和-592位点的等位基因频率分布存在显著差异（p = 0.036，OR = 1.134，95% CI 0.999 - 1.287以及p = 0.036，OR = 1.134，95% CI 0.999 - 1.287）。经Bonferroni校正后，多态性与AR之间无显著差异（p > 0.05）。此外，HBV复发患者和非HBV复发患者之间的总体基因型分布也无显著差异（p > 0.05）。
我们的研究表明，IL10、TNFα和TGFβ1的基因多态性在LT后AR和HBV复发中不具有主要独立作用，可能不是中国肝移植受者LT后AR和HBV复发的危险因素。
