Variability in the leptin receptor gene and other risk factors for post-transplant diabetes mellitus in renal transplant recipients

Aim: Post-transplant diabetes mellitus (PTDM) is one of the main complications after kidney transplantation. It is known that leptin plays an important role in glucose metabolism and mutations in the leptin receptor gene (LEPR) are responsible for different complications in renal transplant recipients. We aimed to analyse the association of polymorphisms in LEPR with the development of PTDM in these patients. Methods: A total of 315 renal transplant recipients were genotyped for the Lys109Arg, Gln223Arg and Lys656Asn polymorphisms. The impact of these genetic variables together with other clinical and demographic parameters on PTDM risk was evaluated in a multivariate regression analysis. Results: The 223Arg variant showed a significant association with PTDM risk [OR = 3.26 (1.35-7.85), p = 0.009] after correcting for multiple testing. Carriers of this variant also showed higher BMI values (26.95 +/- 4.23) than non-carriers (25.67 +/- 4.43, p = 0.025). In addition, it was BMI at transplant and not the BMI increment in the first year after grafting that was associated with PTDM (p > 0.00001). Haplotype analyses did not reveal significant associations. Conclusions: Our result show, for the first time to our knowledge, that genetic variability in the LEPR may contribute significantly to the risk for PTDM in renal transplant recipients.KEY MESSAGES The LEPR Gln223Arg polymorphism significantly contributes to the development of PTDM in renal transplant recipients. The effect of the 223Arg variant on PTDM is strongly modulated by the age of the recipient. The 223Arg variant in the leptin receptor is related to higher BMI in renal transplant recipients.