Recipient cytotoxic T lymphocyte antigen-4 +49 G/G genotype is associated with reduced incidence of hepatitis B virus recurrence after liver transplantation among Chinese patients.
BACKGROUND
Single-nucleotide polymorphisms (SNP) of two-gene locus cytotoxic T lymphocyte antigen-4 (CTLA-4) +49 and CD86 +1057 were previously reported to influence the outcome of liver transplantation (LT) with respect to allograft acceptance. SNP at CTLA-4 +49 was also suggested to be associated with the individual difference in the clearance of hepatitis B virus (HBV). However, their influence on the incidence of post-LT HBV reinfection was not clear. With the increasing knowledge of costimulatory mechanisms on LT and host immune response, we designed this study to investigate the relationship between different alleles as well as genotypes at these two locations and HBV reinfection after LT.


METHODS
Genomic DNA from 167 LT recipients with HBV-related diseases was genotyped for CTLA-4 +49 and CD86 +1057 genomic polymorphisms using a sequence-specific primer-polymerase chain reaction (PCR-SSP). HBV recurrence was diagnosed based on the serological and pathological finding of HBV DNA and HBsAg.


RESULTS
The present study indicated that the recipients with CTLA-4 +49 GG genotype had a reduced risk (6.67%) of HBV recurrence compared with non-CTLA-4 +49 GG-carrying individuals (20.7%) (relative risk 3.098) (P=0.032). The allelic frequency of CTLA-4 +49 G was also significantly lower in patients with HBV recurrence, compared with that in patients without HBV recurrence (P=0.013, odds ratio 2.176, 95% confidence interval 1.170-4.046). However, no significant association was found between CD86 +1057 and HBV recurrence.


CONCLUSIONS
Our result on CTLA-4 +49 A/G polymorphism indicated that the CTLA-4 +49 GG genotype was related to a reduced risk in the incidence of HBV recurrence.
Jiang
Zhijun
Z
Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Department of Hepatobiliary Surgery, the First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, China.
Feng
Xiaoning
X
Zhang
Wu
W
Gao
Feng
F
Ling
Qi
Q
Zhou
Lin
L
Xie
Haiyang
H
Chen
Qixing
Q
Zheng
Shusen
S
D015703:Antigens, CD / Q000235:genetics*; D000943:Antigens, Differentiation / Q000235:genetics*; D044466:Asian People / Q000208:ethnology; D051940:B7-2 Antigen / Q000235:genetics; D060908:CTLA-4 Antigen; D005260:Female; D005838:Genotype; D006085:Graft Survival; D006509:Hepatitis B / Q000453:epidemiology* / Q000235:genetics; D006515:Hepatitis B virus / Q000472:pathogenicity*; D006801:Humans; D015994:Incidence; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D012008:Recurrence
D015703:Antigens, CD; D000943:Antigens, Differentiation; D051940:B7-2 Antigen; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human