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

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 receivedkidneytransplantsbetween1989and2007, withoutahistoryofdiabetesandwithapretransplant 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.