Increased body mass index after kidney transplantation in activating transcription factor 6 single polymorphism gene...

Endoplasmic reticulum stress has been implicated in the pathogenesis of new-onset diabetes after transplantation (NODAT) and of metabolic disorders. Activated Transcription Factor 6 (ATF6), which is activated during endoplasmic reticulum stress, is involved in lipogenesis and gluconeogenesis. Tacrolimus may induce endoplasmic reticulum stress in pancreatic beta cells. Since studies have demonstrated that single nucleotide polymorphisms (SNPs) of ATF6 are associated with type 2 diabetes, we sought to determine whether their mutations were associated with NODAT among renal transplant recipients treated with tacrolimus.

We genotyped 269 renal transplant recipients using TaqMan assays for allelic discrimination for 6 ATF6 gene polymorphisms: rs10918215, rs7514053, rs1058405, rs4479731, rs2340721, and rs13401. All patients received an immunosuppressive regimen including tacrolimus. We analyzed all previously known risk factors for NODAT.

We could not confirm are association between ATF6 SNP and NODAT. We observed a significant association between ATF6 SNP rs2340721 and increased body weight and body mass index (BMI) both upon univariate and multivariate analyses. The average BMI was higher among patients with 2 mutant SNP2 (rs2340721) alleles (CC) than those with 2 wild-type alleles (AA): 23.8 ± 3.7 versus 25.5 ± 4.4 kg/m2 (P = .02). The odds ratio (95% confidence interval [CI]) for BMI associated with the CC genotype was 2.43 (1.16-5.09; P = .02).

ATF6 polymorphisms were not associated with NODAT among our population of renal transplant recipients treated with tacrolimus. However, these data underscore the role of ATF6 and endoplasmic reticulum stress in the regulation of metabolic flux among patients treated with tacrolimus, suggesting that inherited disturbances of endoplasmic reticulum stress signaling could predispose people to obesity.