Chakkera H A, Hanson R L, Raza S M, DiStefano J K, Millis M P, Heilman R L, Mulligan D C, Reddy K S, Mazur M J, Hamawi K, Moss A A, Mekeel K L, Cerhan J R
Division of Transplantation Medicine, Mayo Clinic, 5777 E. Mayo Blvd., Phoenix, AZ 85259, Arizona, USA.
Transplant Proc. 2009 Dec;41(10):4172-7. doi: 10.1016/j.transproceed.2009.08.063.
New-onset diabetes mellitus, which occurs after kidney transplant and type 2 diabetes mellitus (T2DM), shares common risk factors and antecedents in impaired insulin secretion and action. Several genetic polymorphisms have been shown to be associated with T2DM. We hypothesized that transplant recipients who carry risk alleles for T2DM are "tipped over" to develop diabetes mellitus in the posttransplant milieu.
We investigated the association of genetic and traditional risk factors present before transplantation and the development of new-onset diabetes mellitus after kidney transplantation (NODAT). Markers in 8 known T2DM-linked genes were genotyped using either the iPLEX assay or allelic discrimination (AD)-PCR in the study cohort testing for association with NODAT. We used univariate and multivariate logistic regression models for the association of pretransplant nongenetic and genetic variables with the development of NODAT.
The study cohort included 91 kidney transplant recipients with at least 1 year posttransplant follow-up, including 22 who developed NODAT. We observed that increased age, family history of T2DM, pretransplant obesity, and triglyceridemia were associated with NODAT development. In addition, we observed positive trends, although statistically not significant, for association between T2DM-associated genes and NODAT.
These findings demonstrated an increased NODAT risk among patient with a positive family history for T2DM, which, in conjunction with the observed positive predictive trends of known T2DM-associated genetic polymorphisms with NODAT, was suggestive of a genetic predisposition to NODAT.
肾移植后新发糖尿病与2型糖尿病(T2DM)在胰岛素分泌和作用受损方面具有共同的危险因素和前驱因素。已有多项基因多态性被证明与T2DM相关。我们推测,携带T2DM风险等位基因的移植受者在移植后的环境中“易患”糖尿病。
我们调查了移植前存在的遗传和传统危险因素与肾移植后新发糖尿病(NODAT)发生之间的关联。在研究队列中,使用iPLEX分析或等位基因鉴别(AD)-PCR对8个已知的与T2DM相关基因中的标记进行基因分型,以检测其与NODAT的关联。我们使用单变量和多变量逻辑回归模型来分析移植前非遗传和遗传变量与NODAT发生之间的关联。
研究队列包括91名肾移植受者,移植后至少随访1年,其中22人发生了NODAT。我们观察到,年龄增加、T2DM家族史、移植前肥胖和高甘油三酯血症与NODAT的发生有关。此外,我们观察到T2DM相关基因与NODAT之间存在正相关趋势,尽管在统计学上不显著。
这些发现表明,T2DM家族史阳性的患者发生NODAT的风险增加,这与观察到的已知T2DM相关基因多态性对NODAT的阳性预测趋势相结合,提示NODAT存在遗传易感性。