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男性及绝经后女性雌激素受体基因多态性与糖尿病大血管病变的关系 被引量:7

Association of Estrogen Receptor Gene Polymorphisms with Macroangiopathy and Lipid Levels in Men and Postmenopausal Women with Type 2 Diabetes Mellitus
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摘要 本文应用聚合酶链反应和限制片长多态性方法测定 118例男性及绝经后女性 2型糖尿病患者和 32例正常对照者的雌激素受体基因型 ,结合血清雌激素及血脂水平 ,分析了其与大血管病变的相关性。研究发现 ,雌激素受体等位基因X、x、P和p频率在糖尿病组为 0 .2 0 8、0 .792、0 .4 32和 0 .5 6 8;在对照组分别为 0 .2 6 6、0 .734、0 .5 0和0 .5 0。基因型频率分布符合Hardy Weinberg平衡定律。XbaI酶切多态性基因型、等位基因频率及结合XbaI和PvuⅡ两个酶切多态性分析在组内、组间比较差异均无显著性。PvuⅡ突变型频率在颈动脉内膜中膜厚度增厚组显著增高。糖尿病组Xx型的总胆固醇和低密度脂蛋白胆固醇水平明显高于xx型 ,脑血管病变组的雌激素水平较无大血管病变组明显增高 ,XbaI和PvuⅡ突变型分别与总胆固醇和低密度脂蛋白胆固醇水平呈显著的正相关。PvuⅡ酶切位点突变是大血管病变的独立危险因素。此结果提示 ,男性和绝经后女性糖尿病人群的雌激素受体基因突变可能导致血脂水平的变化 ,雌激素水平增高可能与脑血管终点事件有关。XbaI酶切多态性与糖尿病合并大血管病变无相关性 ,而PvuⅡ酶切多态性的突变可能是大血管病变的危险因素之一。 Aim To analyze if the mutation of estrogen receptor (ER) gene has any relationship with macroangiopathy (MA) in men and postmenopausal women with type 2 diabetes (T2DM). Methods ER genotyping was performed by using PCR-RFLP method in 118 T2DM patients with and without MA and 32 normal controls (NC), which were men and postmenopausal women. The serum E2 and lipid levels were also determined. Results ER allelic frequencies of X, x and P,p alleles were 0.208, 0.792; 0.432, 0.568 and 0.266, 0.734; 0.50, 0.50 in T2DM group and control group respectively. There was no significant difference in frequencies of allele and genotype in XbaI polymorphism or XbaI with PvuⅡ polymorphisms together between these two groups. The Pp and PP genotypes were significantly more frequent in subjects with IMT>1.0 mm than in those without MA (86.7% vs 58.3%, P<0.05). In subjects of T2DM, serum TC and LDLC levels were significantly higher in subjects with the Xx genotype compared with those with the wild genotypes [(5.33±1.06) mmol/L vs (4.81±0.99) mmol/L P<0.01; (3.43±0.72) mmol/L vs (3.08±0.8) mmol/L P<0.05 respectively]. The serum E2 level was significantly higher in CVD group than group without MA [(34.59±16.8) ng/L vs (26.46±11.98) ng/L, P<0.05]. The mutation genotypes of XbaI and PvuⅡ were significantly and positively correlated with TC and LDLC levels respectively (r=0.2671 P=0.005 and r=0.2483 P=0.010; r=0.2301 P=0.017 and r=0.2172 P=0.024 respectively). The PvuⅡ polymorphism was the independent risk factor for MA (OR=2.996, 95%CI 1.023~8.767, P=0.041). Conclusion The mutation of ER gene in men and postmenopausal women with T2DM might result in the change of serum lipid levels. The higher E2 level might have the relationship with the endpoint of CVD. XbaI polymorphism is not related with MA, but PvuⅡ polymorphism might be a risk factor for MA in men and postmenopausal women with T2DM.
出处 《中国动脉硬化杂志》 CAS CSCD 2004年第2期189-193,共5页 Chinese Journal of Arteriosclerosis
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