Polymorphisms in cytokine genes and their association with acute rejection and recurrence of hepatitis B in Chinese liver transplant recipients.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Xie
Hai Yang
HY
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.
Wang
Wei Lin
WL
Yao
Min Ya
MY
Yu
Song Feng
SF
Feng
Xiao Ning
XN
Jin
Jing
J
Jiang
Zhi Jun
ZJ
Wu
Li Ming
LM
Zheng
Shu Sen
SS
D044466:Asian People; D016207:Cytokines / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006084:Graft Rejection / Q000235:genetics*; D006239:Haplotypes; D006509:Hepatitis B / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D016031:Liver Transplantation; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10