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

Yu-Zheng Ge; Ran Wu; Tian-Ze Lu; Rui-Peng Jia; Ming-Hao Li; Xiao-Fei Gao; Xiao-Min Jiang; Xian-Bo Zhu; Liang-Peng Li; Si-Jia Tan; Qun Song; Wen-Cheng Li; Jia-Geng Zhu

doi:10.1371/journal.pone.0093938

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

PLoS One. 2014 Apr 4;9(4):e93938. doi: 10.1371/journal.pone.0093938. eCollection 2014.

Authors

Affiliations

¹ Center for Renal Transplantation, Nanjing First Hospital, Nanjing Medical University, Nanjing, China; Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
² Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
³ Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
⁴ Department of Cardiothoracic Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

Abstract

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.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

MeSH terms

Graft Rejection / genetics*
Haplotypes / genetics
Humans
Odds Ratio
Organ Transplantation / adverse effects*
Polymorphism, Single Nucleotide / genetics*
Transforming Growth Factor beta1 / genetics*

Substances

TGFB1 protein, human
Transforming Growth Factor beta1

Grants and funding

This project was supported by grants from the National Natural Science Foundation of China (81070597, 81370853), Science and Education Development Program of the Jiangsu Province Health Board (LJ201107), Six Talent Peaks of the Jiangsu Province Health Bureau (2011-WS-093) and Research and Innovation Program for Graduates of Jiangsu Province (CXZZ13_0583). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.