The Center for Human Nutrition, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
Metab Syndr Relat Disord. 2011 Feb;9(1):25-9. doi: 10.1089/met.2010.0041. Epub 2010 Oct 19.
Diabetes mellitus is a major cause of morbidity and mortality among transplanted patients. This study evaluated the role of the ENPP1 K121Q polymorphism and other variables known to affect diabetes risk in 115 nondiabetic and unrelated patients who underwent kidney transplant at our institution and had consented for use of genetic material (30% whites, 48% blacks, and 22% Hispanics). Thirty-six of these patients (30%) developed posttransplant diabetes mellitus (PTDM) within 1 year of observation from transplant. Black race, ENPP1 K121Q polymorphism, age, body mass index (BMI), and immunosuppressive medications were found to have the strongest associations with PTDM in the logistic regression and receiver operator characteristic (ROC) analysis. However, because ENPP1 K121Q is more common in Hispanics and in blacks, who also have higher PTDM prevalence, the studied genetic polymorphism did not exert independent predictive effect, whereas ethnicity, specifically black versus non-black, was the most robust predictor of PTDM. The model with the largest ROC area under the curve (AUC) of 0.80 was comprised of black/non-black, age, BMI, and tacrolimus treatment as significant predictors. A reduced model containing only ethnicity (black/non-black) and age as predictors yielded similar results (ROC AUC 0.78). We conclude that black race and age are major and not modifiable risk factors for PTDM. The specific role of ENPP1 K121Q on ethnic susceptibility to PTDM deserves further investigation in larger cohorts of transplanted patients.
糖尿病是移植患者发病率和死亡率的主要原因。本研究评估了在我院接受肾移植且同意使用遗传物质的 115 名非糖尿病和非相关患者中,已知影响糖尿病风险的 ENPP1 K121Q 多态性和其他变量的作用(30%为白人,48%为黑人,22%为西班牙裔)。这些患者中有 36 名(30%)在移植后 1 年内发生了移植后糖尿病(PTDM)。在逻辑回归和接受者操作特征(ROC)分析中发现,黑种人、ENPP1 K121Q 多态性、年龄、体重指数(BMI)和免疫抑制药物与 PTDM 有最强的关联。然而,由于 ENPP1 K121Q 在西班牙裔和黑人群体中更为常见,而这些人群的 PTDM 患病率也较高,因此所研究的遗传多态性并未产生独立的预测作用,而种族,特别是黑种人与非黑种人之间的差异是 PTDM 的最强预测因素。ROC 曲线下面积(AUC)最大的模型(0.80)由黑种人/非黑种人、年龄、BMI 和他克莫司治疗作为重要预测因素组成。包含仅种族(黑种人/非黑种人)和年龄作为预测因素的简化模型也产生了类似的结果(ROC AUC 0.78)。我们得出结论,黑种人和年龄是 PTDM 的主要且不可改变的危险因素。ENPP1 K121Q 在不同种族易感性方面的具体作用值得在更大的移植患者队列中进一步研究。