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基因多态性与台湾肾移植受者移植后糖尿病有关。

Gene polymorphisms are associated with posttransplantation diabetes mellitus among Taiwanese renal transplant recipients.

作者信息

Weng S-C, Shu K-H, Tarng D-C, Wu M-J, Chen C-H, Yu T-M, Chuang Y-W, Huang S-T, Cheng C-H

机构信息

Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

出版信息

Transplant Proc. 2012 Apr;44(3):667-71. doi: 10.1016/j.transproceed.2011.11.011.

Abstract

BACKGROUND

Genetic variations may affect posttransplantation metabolic syndrome and diabetes mellitus (PTDM), which is associated with greater morbidity and progressive impairment of both patient and graft survivals. The aim of this study was to evaluate several candidate gene polymorphisms for their association with the risk of developing PTDM.

METHODS

In April 1999, we enrolled 278 renal transplant participants, including 251 subjects free of diabetes and 27 with PTDM. We studied several candidate gene polymorphisms associated with diabetes: 4G/5G polymorphism of plasminogen activator inhibitor 1 (PAI-1) at -675; C/T polymorphism of interleukin-1beta (IL-1β) at -511; G/C polymorphism of IL-6 at 174; polymorphic XbaI of Glucose transporter 1 (GLUT1); and C/T polymorphism of methylenetetrahydrofolate redutase (MTHFR) at 677.

RESULTS

The PTDM group had an older mean age (47.6 ± 9.8 years), greater predominance of men (77.8%), higher number of chronic diseases (CDN ≥2, 96.3%), and more patients using tacrolimus-based immunosuppression (44.4%; P < .05). Using model A, a simple logistic regression, we observed that patients with the IL-6 G/G genotype experienced a lower risk of developing PTDM (odds ratio [OR], 0.08; 95% confidence interval [CI] 0.01-0.86), and multiple logistic regression models B and C, after adjusting for different variables, confirmed this observation (model B: OR, 0.05; 95% CI, 0.00-0.66). The IL-6 G/G genotype showed a borderline effect in model C (OR, 0.02; 95% CI, 0.00-1.16). There were no significant differences between the 2 groups in genotype variations of PAI-1, IL-1β, GLUT-1, and MTHFR.

CONCLUSIONS

The G/G genotype of IL-6 may play an important role to lower the risk for PTDM development.

摘要

背景

基因变异可能影响移植后代谢综合征和糖尿病(PTDM),这与更高的发病率以及患者和移植物存活率的渐进性损害相关。本研究的目的是评估几种候选基因多态性与发生PTDM风险的关联。

方法

1999年4月,我们招募了278名肾移植参与者,包括251名无糖尿病的受试者和27名患有PTDM的受试者。我们研究了几种与糖尿病相关的候选基因多态性:纤溶酶原激活物抑制剂1(PAI-1)-675处的4G/5G多态性;白细胞介素-1β(IL-1β)-511处的C/T多态性;IL-6 174处的G/C多态性;葡萄糖转运蛋白1(GLUT1)的XbaI多态性;以及亚甲基四氢叶酸还原酶(MTHFR)677处的C/T多态性。

结果

PTDM组的平均年龄较大(47.6±9.8岁),男性占比更高(77.8%),慢性病数量更多(CDN≥2,96.3%),且更多患者使用基于他克莫司的免疫抑制治疗(44.4%;P<.05)。使用模型A(简单逻辑回归),我们观察到IL-6 G/G基因型的患者发生PTDM的风险较低(优势比[OR],0.08;95%置信区间[CI] 0.01-0.86),在调整不同变量后的多个逻辑回归模型B和C证实了这一观察结果(模型B:OR,0.05;95%CI,0.00-0.66)。IL-6 G/G基因型在模型C中显示出临界效应(OR,0.02;95%CI,0.00-1.16)。PAI-1、IL-1β、GLUT-1和MTHFR的基因型变异在两组之间无显著差异。

结论

IL-6的G/G基因型可能在降低PTDM发生风险中起重要作用。

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