血管内皮生长因子基因3'-非翻译区936C/T多态性与2型糖尿病外周神经病变相关

目的 探讨血管内皮生长因子(VEGF)基因3'-非翻译区936C/T多态性与山东地区汉族人2型糖尿病合并周围神经病变(DPN)之间的关系.方法 194例糖尿病患者分为单纯糖尿病组(n=92)和糖尿病神经病变组(n=102),另120名健康个体设为健康对照组.采用PCR-限制性片段长度多态性(RFLP)方法确定全部个体的基因型;对不同基因型间及病例组间的临床与生化参数、血清VEGF浓度以及VEGF基因936C/T多态性进行了统计分析.结果 糖尿病神经病变组C等位基因及CC基因型频率显著高于对照组(x2为9.406和9.677,P＜0.05)和糖尿病组(x2为5.578和5.614,P＜0.05),而携带T等位基因的基因型(CT+TT)频率及T等位基因频率显著低于对照组(x2为9.406和9.677,P＜0.05)和糖尿病组(x2为5.578和5.614,P＜0.05).Logistic多元回归分析显示血清低密度脂蛋白胆固醇(LDL-C)、总胆固醇、HbA1c水平以及VEGF浓度与DPN发生呈正相关,而VEGF基因936C/T多态性与糖尿病周围神经病变发病危险呈负相关(β=-1.046,OR=0.457,P=0.006,95%CI:0.166～0.741).结论 中国山东地区汉族人群中存在VEGF基因936C/T多态性,C等位基因及CC基因型患者可能是糖尿病易于发生神经病变危险性的遗传标志,而T等位基因和携带T等位基因的基因型(936TF基因型和936CT基因型)可能是降低糖尿病发生神经病变风险的遗传标志.

Abstract：

Objective To elucidate the relationship between a 936C/T mutation at 3'-untranslated region of human vascular endothelial growth factor(VEGF) gene and diabetic peripheral neuropathy ( DPN ). Methods All subjects recruited in this study were assigned into DM (n = 92, diabetes without neuropathy, retinopathy or nephropathy), DPN (n = 102, diabetes with peripheral neuropathy only ), and healthy control (n = 120 ) groups,respectively. The gene polymorphism was determined by PCR-RFLP, as well as the other clinical parameters including serum VEGF by ELISA. Results The frequencies of both genotype CC and allele C were significantly higher in DPN group than those in either DM group(x2 = 5.578 and 5.614, P＜0. 05 ) or control group (x2 = 9. 406 and 9. 677, P＜0. 05 ). However, the frequencies of genotype(CT+TT) and allele T were significantly lower in DPN group than that in either DM group(x2 =5.578 and 5.614, P＜0. 05) and control group (x2=9.406 and 9.677, P＜0.05). The multivariate logistic regression analysis showed that the levels of HbA1c, total cholesterol, low-density lipoproteincholesterol( LDL-C ), and serum VEGF positively correlated with DPN, while the 936C/T polymorphism of VEGF gene negatively correlated with DPN(β= -1. 046, OR=0. 457, P=0. 006, 95% CI: 0. 166-0. 741 ). Conclusions Allele 936C of VEGF gene may serve as a genetic marker susceptible to DPN, while allele 936T may be a protective genetic marker of DPN.

Association between the 936C/T polymorphism in the 3'-untranslated region of vascular endothelial growth factor gene and diabetic peripheral neuropathy in China

Objective To elucidate the relationship between a 936C/T mutation at 3'-untranslated region of human vascular endothelial growth factor(VEGF) gene and diabetic peripheral neuropathy ( DPN ). Methods All subjects recruited in this study were assigned into DM (n = 92, diabetes without neuropathy, retinopathy or nephropathy), DPN (n = 102, diabetes with peripheral neuropathy only ), and healthy control (n = 120 ) groups,respectively. The gene polymorphism was determined by PCR-RFLP, as well as the other clinical parameters including serum VEGF by ELISA. Results The frequencies of both genotype CC and allele C were significantly higher in DPN group than those in either DM group(x2 = 5.578 and 5.614, P＜0. 05 ) or control group (x2 = 9. 406 and 9. 677, P＜0. 05 ). However, the frequencies of genotype(CT+TT) and allele T were significantly lower in DPN group than that in either DM group(x2 =5.578 and 5.614, P＜0. 05) and control group (x2=9.406 and 9.677, P＜0.05). The multivariate logistic regression analysis showed that the levels of HbA1c, total cholesterol, low-density lipoproteincholesterol( LDL-C ), and serum VEGF positively correlated with DPN, while the 936C/T polymorphism of VEGF gene negatively correlated with DPN(β= -1. 046, OR=0. 457, P=0. 006, 95% CI: 0. 166-0. 741 ). Conclusions Allele 936C of VEGF gene may serve as a genetic marker susceptible to DPN, while allele 936T may be a protective genetic marker of DPN.