Variants of the adiponectin and adiponectin receptor-1 genes and posttransplantation diabetes mellitus in renal allograft recipients

J Clin Endocrinol Metab. 2012 Jan;97(1):E129-35. doi: 10.1210/jc.2011-1796. Epub 2011 Nov 2.

Abstract

Context: Posttransplantation diabetes mellitus (PTDM) is a major metabolic complication in renal transplant recipients. Adiponectin (ADIPOQ) and adiponectin receptor-1 (ADIPOR1) gene polymorphisms have been associated with type 2 diabetes. However, it is unknown whether these polymorphisms are also risk factors for PTDM.

Objective: We investigated the association between PTDM and single-nucleotide polymorphisms of ADIPOQ and ADIPOR1 in a cohort of renal allograft recipients.

Design, setting, and participants: Five hundred seventy-five patients (367 men and 208 women) who received kidney transplants between 1989 and 2007, without a history of diabetes and with a pretransplant fasting glucose concentration less than 5.5 mmol/liter. Patients were followed up for a median 10 yr. Genotypes included single-nucleotide polymorphisms of the following: ADIPOQ rs266729, rs822395, rs822396, rs2241766, and rs1501299 and ADIPOR1 rs2232853, rs12733285, and rs1342387.

Results: TT-homozygotes in ADIPOQ rs1501299 [hazard ratio (HR) = 1.70, P = 0.032] had greater risk of PTDM after adjusting for age, sex, amount of weight gain, and type of immunosuppressant. There was a significant interaction between sex and ADIPOQ rs1501299 genotype (P = 0.037). In men, but not in women, TT-homozygotes in ADIPOQ rs1501299 were more likely to develop PTDM than the wild GG-homozygotes (HR = 2.50, P = 0.002), whereas GT-heterozygotes had nonsignificantly elevated risk (HR = 1.41, P = 0.128).

Conclusion: Genetic variation in ADIPOQ rs1501299 is associated with PTDM in a sex-specific manner.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / genetics
  • Adult
  • Diabetes Mellitus / etiology*
  • Diabetes Mellitus / genetics
  • Female
  • Follow-Up Studies
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide* / physiology
  • Receptors, Adiponectin / genetics*
  • Sex Factors
  • Transplantation, Homologous

Substances

  • ADIPOQ protein, human
  • ADIPOR1 protein, human
  • Adiponectin
  • Receptors, Adiponectin