TGF-β1 and TSC-22 gene Polymorphisms and susceptibility to microvascular complications in type 2 diabetes
TGF-β1 and TSC-22 gene Polymorphisms and susceptibility to microvascular complications in type 2 diabetes
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DOI：
10.1159/000104874
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发表时间：
2007-01-01
影响因子：
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通讯作者：
Ksiazek, Andrzej
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文献类型：
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作者：
Buraczynska, Monika;Baranowicz-Gaszczyk, Iwona;Ksiazek, Andrzej
背景/目的：有强有力的证据表明遗传因素与糖尿病微血管并发症有关。本研究的目的是探讨TGF-β 1（转化生长因子β 1）和TSC-22（转化生长因子β刺激克隆22）基因的分子变异体在2型糖尿病肾病和糖尿病视网膜病变中的作用。方法：采用病例对照研究方法，对503例患者和400例健康体检者进行研究。采用聚合酶链反应和限制性片段长度多态性方法对DNA样本进行基因分型。结果：糖尿病肾病245例，视网膜病变195例，无并发症168例。对所有受试者进行TGF-β 1基因T869 C和C-509 T多态性以及TSC-22基因-396多态性的基因分型。在肾病和视网膜病变患者中观察到T869 C多态性的CC基因型频率显著增加（分别为33%和48%，对照组和无并发症患者分别为19%和15%）。C等位基因的频率也较高（肾病为0.58，视网膜病变为0.64，对照组为0.42）。TSC-22多态性的G等位基因与糖尿病肾病风险增加相关（在无并发症患者和对照组中，频率分别为0.15 vs. 0.07和0.06）。在TSC-22多态性的G等位基因和TGF-β多态性的C等位基因之间观察到相互作用。结论：我们的数据提示TGF-β T869 C基因多态性与2型糖尿病患者肾病和视网膜病变风险增加相关。它与参与TGF-β信号通路的TSC-22基因相互作用，促进糖尿病肾病的发展。
Background/Aim: There is a strong evidence for the involvement of genetic factors in diabetic microvascular complications. The aim of our study was to investigate the role of molecular variants of the TGF-beta 1 ( transforming growth factor beta 1) and the TSC-22 ( transforming growth factor beta stimulated clone 22) genes in diabetic nephropathy and diabetic retinopathy in type 2 diabetes. Methods: A case-control study was conducted in 503 patients and 400 healthy subjects. DNA samples were genotyped by polymerase chain reaction and restriction fragment length polymorphism methods. Results: Among the patients, 245 had diabetic nephropathy, 195 had retinopathy, and 168 were free from complications. All subjects were genotyped for T869C and C-509T polymorphisms of the TGF-beta 1 gene and for - 396 polymorphism of the TSC-22 gene. A significantly increased frequency of the CC genotype of the T869C polymorphism was observed in patients with nephropathy and retinopathy ( 33 and 48%, respectively, vs. 19 and 15%, respectively, in controls and patients free from complications).The frequency of the C allele was also higher ( 0.58 for nephropathy and 0.64 for retinopathy vs. 0.42 in controls). The G allele of the TSC-22 polymorphism was associated with an increased risk of diabetic nephropathy ( frequency 0.15 vs. 0.07 and 0.06, respectively, in patients free from complications and controls). An interaction was observed between the G allele of the TSC-22 polymorphism and the C-allele of the TGF-beta polymorphism. Conclusions: Our data suggest the association of TGF-beta T869C gene polymorphism with an increased risk of nephropathy and retinopathy in type 2 diabetes patients. It interacts with the TSC-22 gene involved in the TGF-beta signaling pathway, promoting the development of diabetic nephropathy.