2型糖尿病患者大脑中动脉狭窄与肾素-血管紧张素系统基因多态性的关系

目的 探讨大脑中动脉(MCA)狭窄与肾素-血管紧张素系统(renin angiotensin system,RAS)基因多态性的关系。方法 对2202个汉族2型糖尿病人用经颅多普勒(transcranial Doppler,TCD)筛选,MCA狭窄者为病例组,其余为对照组,然后经年龄、性别、糖尿病病程配对后选择病例组218例,对照组489例,用PCR、PCR-RFLP检测ACE、ATIR、AGT基因型。结果 病例组和对照组的三种基因的基因型、等位基因频率分布无差异;但在AGT基因的基因型为TT时,病例组的ACE基因的ID、DD基因型比例较高(P<0.1,OR=1.40),而在ACE基因的基因型为ID、DD时,病例组的AGT基因的TT基因型比例也较高(P<0.05,OR=1.71);在ATIR基因的基因型为AA时,病例组的AGT基因的TT基因型比例较高(P<0.1,OR=1.66)。结论 RAS单个基因的多态性与MCA狭窄不相关,但RAS的几个基因之间的相互作用与MCA狭窄有关。

Renin angiotensin system gene polymorphisms and middle cerebral artery stenosis in Chinese patients with type 2 diabetes mellitus

Objective To investigate the contributions of three renin angiotensin system (RAS) gene polymorphisms to the presence of middle cerebral artery (MCA) stenosis in Chinese patients with type 2 diabetes mellitus. Subjects and Methods This was an age, gender and duration of diabetes matched case-control study. All 2202 consecutive Type 2 diabetic patients were examined by transcranial Doppler (TCD) . Of all 2202 diabetic patients without stoke or TIA, 292 patients were excluded from this study because it was not possible for insonalion of the cerebral arteries through the temporal window, and 389 patients with MCA stenosis were identified, the other 1521 diabetic patients were considered as control. The polymorphisms of ACE, AT1R, and AGT genes were identified on the basis of polymerase-chain-reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP) . Results There were no significant differences in the genotype and allele frquencies of the RAS polymorphisms between the patients with and without MCA stenosis in matched groups. However, we found a slightly significant interaction ( P < 0.1, OR = 1.66) between AT1R and AGT gene polymorphisms on the risk of MCA stenosis. The association between the AGT TT genotype and MCA stenosis was restricted to the subjects with AT1R AA genotype. Similarly, there was a significant interaction between ACE and AGT gene polymorphisms on the risk of MCA stenosis. The association ( P < 0.05, OR = 1.71) between AGT TT genotype and MCA stenosis was restricted to the subjects carrying ACE D/allele, whereas the association ( P < 0.1, OR = 1.40) between the ACE ID or DD genotype and MCA stenosis was restricted to the subjects with the AGT TT genotype. Conclusions The single RAS gene polymorphism was not associated with MCA stenosis in either the total or the age, gender and diabetic duration-matched groups. However, There was a significant interaction between ACE and AGT gene polymorphisms on the risk of MCA stenosis. Similar finding was seen in the interaction between AT1R and AGT gene polymorphisms.