Ⅱ型糖尿病并发肾病患者Apo E基因多态性研究

Study on apolipoprotein E polymorphism in type diabetes mellitus patients with nephropathy

目的研究糖尿病肾病（ＤＮ）发生、发展的遗传学倾向，寻找与ＤＮ发病有关的基因。方法采用ＰＣＲＲＥＬＰ技术，研究了９７例Ⅱ型糖尿病（ＤＭ）患者ＡｐｏＥ基因多态性与ＤＮ及其脂代谢异常的关系。结果（１）ＤＮ组ε２等位基因频率明显高于糖尿病组（Ｐ＜００１）及正常组（Ｐ＜０００５）；在尿白蛋白排泄率＞２００μｇ／ｍｉｎ组和２０～２００μｇ／ｍｉｎ组之间ＡｐｏＥ基因频率无明显差异。（２）携ε２等位基因的ＤＭ患者甘油三酯（ＴＧ）水平明显高于携ε３组（Ｐ＜００５），而胆固醇Ｃｈｏｌ（Ｐ＜０００１），低密度脂蛋白（ＬＤＬ）（Ｐ＜００１）则明显低于携ε３组；同时ε２组出现蛋白尿的比率及在ＤＮ时发生脂代谢异常的比率均增加，但无统计学意义。（３）携ε３的ＤＭ组ＡｐｏＡ水平比ε２，ε４组均明显升高（Ｐ＜００５）。（４）在全部ＤＭ患者中ε２等位基因频率女性高于男性（Ｐ＜００２５），但在ＤＮ患者中携ε２等位基因频率无性别差异。（５）Ａｐｏε２等位基因含量与ＤＮ发生率有关，ε２纯合子发生ＤＮ的比率较非ε２携带者明显增加（Ｐ＜００５）。结论ＡｐｏＥ基因多态性与ＤＮ发生有关，ε２等位基因频率越高，发生ＤＮ的可能性越大，并且ＤＮ?

Objective In order to confirm the tendency of heredity in DN,and to find out the related genes. Methods The association of Apo E genetic polymorphism,diabetic nephropathy (DN) and lipid abnormalities was investigated in 97 type diabetic(DM) patients with technique of PCRRFLP. Results (1)Apo E2 allele frequency was significantly higher in DN patients than in DM patients with normoalbuminuria(P<001),and than in health subjects(P<0005).Apo E genetic freqency was not significantly different between the group of albuminuia>200 g/min and the group of albuminuia 20200 g/min. (2)DM patients with 2 had significantly higher level of plasma trigyceride(TG),and significantly lower levels of plasma total cholesterol(Tchol),low density lipoprotein(LDL)compared with that with 3;(3)Apo A level was significantly higher in DM patients with 3 than those with 2 and 4(P<005);(4)In all DM patients 2 allele frequency is higher in women than in man(P<0025),but in DN patients Apo E allele frgquency was not different between men and women.(5)The concentration of Apo E2 allele gene was associated with incidence of DN,the incidence of DN in DM patients with E2/2 was significantly increased compared with that without 2(P<005). Conclusion ApoE genetic polymorphism is associated with diabetic nephropathy.The higher allele frequency is,the more possibly DN happens.Onset of DN is connected with the concentration of E2,DM patients with E2/2 all suffer from DN;2 allele frequency is associated with the lipids abnormality,and 2 may aggravated lipid abnormalities in DN patient.Apo E may be interrelated with Apo A.In addition,Apo E genetic polymorphism is also perhaps different between men and women in DM.Apo E2 may be used clinically as an assistant diagnostic index.