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A Variant of the Transcription Factor 7-Like 2 (TCF7L2) Gene and the Risk of Posttransplantation Diabetes Mellitus in Renal Allograft Recipients

¹ Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
² Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
³ Brain Korea 21 for Medical Science, Yonsei University College of Medicine, Seoul, Korea
⁴ Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
⁵ The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
⁶ Department of Preventive Medicine and Public Health, Yonsei University College of Medicine, Seoul, Korea

Address correspondence and reprint requests to Hyun Chul Lee, MD, PhD, Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-Dong Seodaemun-Gu, Seoul, 120-752, Korea. E-mail: endohclee{at}yumc.yonsei.ac.kr; or Soon Il Kim, MD, PhD, Department of Surgery, Yonsei University College of Medicine, 134 Shinchon-Dong Seodaemun-Gu, Seoul, 120-752, Korea. E-mail: soonkim{at}yumc.yonsei.ac.kr

OBJECTIVE—Posttransplantation diabetes mellitus (PTDM) is a major complication associated with kidney transplantation. Defects in insulin secretion play a pivotal role in the pathogenesis of PTDM. A polymorphism in the transcription factor 7-like 2 (TCF7L2) gene was reported to be associated with type 2 diabetes and possibly associated with an insulin secretion defect. The aim of this study was to investigate the association between genetic variations in TCF7L2 and PTDM in renal allograft recipients.

RESEARCH DESIGN AND METHODS—A total of 511 unrelated renal allograft recipients without previously known diabetes were enrolled. Six single nucleotide polymorphisms (rs11196205, rs4506565, rs12243326, rs7903146, rs12255372, and rs7901695) were genotyped in the cohort, which consisted of 119 PTDM patients and 392 non-PTDM subjects. The genotyping of TCF7L2 polymorphisms was performed using real-time PCR.

RESULTS—rs4506565, rs7901695, and rs7903146 were found to be in complete linkage disequilibrium. The rs7903146 genotype distribution was CC 94.3% and CT 5.7%. The incidence of PTDM was significantly higher in patients with the CT genotype than in patients with the CC genotype (41.4 vs. 22.2%) (odds ratio 2.474 [95% CI 1.146–5.341]; P = 0.024). The effect of this genotype remains significant after adjustment for age, sex, amount of body weight gain, and type of immunosuppressant (2.655 [1.168–6.038]; P = 0.020).

CONCLUSIONS—These data suggest that the TCF7L2 rs7903146 genetic variation is associated with an increased risk of PTDM in renal allograft recipients.

Abbreviations: FPG, fasting plasma glucose • MAF, minor allele frequency • PTDM, posttransplantation diabetes mellitus • SNP, single nucleotide polymorphism

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