Leptin receptor gene polymorphisms in kidney transplant patients with post-transplant diabetes mellitus treated with tacrolimus

Int Immunopharmacol. 2023 Nov;124(Pt B):110989. doi: 10.1016/j.intimp.2023.110989. Epub 2023 Sep 28.

Abstract

Post-transplant diabetes mellitus (PTDM) is a metabolic complication that often occurs after kidney transplantation. Factors that increase the risk of this complication are currently being researched, including polymorphisms in genes affecting carbohydrate-lipid metabolism. Leptin is a hormone that affects appetite and adipose tissue and plays an important role in regulating insulin secretion as well as glucose and lipid metabolism. The aim of this study was to examine the association between leptin receptor gene polymorphisms and the development of post-transplant diabetes mellitus in patients treated with tacrolimus. The study was carried out in a group of 201 patients who underwent kidney transplantation. The follow-up period was 12 months. PTDM was diagnosed in 35 patients. Analysing the LEPR gene rs1137101 polymorphism, we observed in patients with PTDM an increased frequency of GG genotype carriers (GG vs AA, OR 3.36; 95 % CI 0.99-11.46; p = 0.04). There were no statistically significant differences in the distribution of the LEPR rs1137100 and LEPR rs1805094 polymorphisms between patients with and without PTDM. Multivariate regression analysis confirmed that female sex, advanced age, increased BMI and a higher number of LEPR rs1137101 G alleles were independent risk factors for PTDM development. The risk of PTDM development was almost 3.5 times greater in LEPR rs1137101 G allele carriers than in AA homozygotes (GG + AG vs AA; OR 3.48; 95 %CI (1.09-11.18), p = 0.035). The results suggest that patients after kidney transplantation with the LEPR gene rs1137101 G allele may have an increased risk of post-transplant diabetes development.

Keywords: Diabetes; Kidney transplantation; Polymorphism; Tacrolimus.

MeSH terms

  • Diabetes Mellitus* / drug therapy
  • Diabetes Mellitus* / genetics
  • Female
  • Humans
  • Kidney Transplantation* / adverse effects
  • Leptin
  • Polymorphism, Genetic
  • Receptors, Leptin / genetics
  • Risk Factors
  • Tacrolimus / adverse effects

Substances

  • Tacrolimus
  • Receptors, Leptin
  • Leptin