TY - JOUR

T1 - Variants of the adiponectin and adiponectin receptor-1 genes and posttransplantation diabetes mellitus in renal allograft recipients

AU - Kang, Eun Seok

AU - Magkos, Faidon

AU - Kim, Beom Seok

AU - Zhai, Rihong

AU - Su, Li

AU - Kim, Yu Seun

AU - Christiani, David C

AU - Lee, Hyun Chul

AU - Mantzoros, Christos S

N1 - (Ekstern)

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Adiponectin/genetics

KW - Adult

KW - Diabetes Mellitus/etiology

KW - Female

KW - Follow-Up Studies

KW - Gene Frequency

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Kidney Transplantation/adverse effects

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide/physiology

KW - Receptors, Adiponectin/genetics

KW - Sex Factors

KW - Transplantation, Homologous

U2 - 10.1210/jc.2011-1796

DO - 10.1210/jc.2011-1796

M3 - Journal article

C2 - 22049178

VL - 97

SP - E129-E135

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 1

ER -