Combined effects of TGFB1 +869 T/C and +915 G/C polymorphisms on acute rejection risk in solid organ transplant recipients: a systematic review and meta-analysis.
BACKGROUND
Transforming growth factor-beta 1(TGF-β1) is involved in the development of acute rejection (AR) episodes in solid organ transplant recipients; and a number of studies have been conducted to investigate the combined effects of human TGF-β1 gene (TGFB1) +869 T/C and +915 G/C polymorphisms on AR risk. However, the results obtained are inconclusive.


METHODS
Eligible studies that investigated the haplotypic association between TGFB1 +869 T/C and +915 G/C polymorphisms and AR risk were comprehensively searched in the PUBMED, EMBASE, China National Knowledge Infrastructure, and Wanfang Database. Statistical analyses were performed by using STATA 12.0 and Review Manager 5.0.


RESULTS
Fourteen eligible studies with 565 AR cases and 1219 non-AR cases were included. Overall, a significantly decreased risk was detected in patients carried with intermediate producer (IP) haplotypes (T/C G/C, T/T G/C, and C/C G/G) and/or low producer (LP) haplotypes (C/C G/C, C/C C/C, T/T C/C, and T/C C/C) compared with high producer (HP) haplotypes (T/T G/G and T/C G/G; IP vs. HP: OR = 0.75, 95% CI, 0.58-0.96, P heterogeneity  = 0.238; IP/LP vs. HP: OR  = 0.77, 95% CI, 0.61-0.98, P heterogeneity  = 0.144). In addition, subgroup analysis by transplant types demonstrated a similar association in patients receiving heart transplant (IP vs. HP: OR  = 0.32, 95% CI, 0.14-0.73, P heterogeneity  = 0.790; IP/LP vs. HP: OR  = 0.41, 95% CI, 0.20-0.85, P heterogeneity  = 0.320).


CONCLUSIONS
The current meta-analysis and systematic review indicated that recipient TGFB1 HP haplotypes were significantly associated with an increased risk for AR in solid organ transplant recipients, particularly patients receiving cardiac allograft.
Center for Renal Transplantation, Nanjing First Hospital, Nanjing Medical University, Nanjing, China; Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Yu-Zheng
YZ
Ge
Center for Renal Transplantation, Nanjing First Hospital, Nanjing Medical University, Nanjing, China; Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Ran
R
Wu
Center for Renal Transplantation, Nanjing First Hospital, Nanjing Medical University, Nanjing, China; Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Tian-Ze
TZ
Lu
Center for Renal Transplantation, Nanjing First Hospital, Nanjing Medical University, Nanjing, China; Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Rui-Peng
RP
Jia
Center for Renal Transplantation, Nanjing First Hospital, Nanjing Medical University, Nanjing, China; Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Ming-Hao
MH
Li
Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Xiao-Fei
XF
Gao
Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Xiao-Min
XM
Jiang
Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Xian-Bo
XB
Zhu
Department of Cardiothoracic Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Liang-Peng
LP
Li
Center for Renal Transplantation, Nanjing First Hospital, Nanjing Medical University, Nanjing, China; Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Si-Jia
SJ
Tan
Center for Renal Transplantation, Nanjing First Hospital, Nanjing Medical University, Nanjing, China; Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Qun
Q
Song
Center for Renal Transplantation, Nanjing First Hospital, Nanjing Medical University, Nanjing, China; Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Wen-Cheng
WC
Li
Center for Renal Transplantation, Nanjing First Hospital, Nanjing Medical University, Nanjing, China; Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Jia-Geng
JG
Zhu
D006084:Graft Rejection / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016017:Odds Ratio; D016377:Organ Transplantation / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1