血小板膜糖蛋白和血管性血友病因子基因多态性及其与血栓性疾病关系研究

The Prevalence of Polymorphisms in the Genes of Platelet Glycoproteins and von Willebrand's factor and its Relevance to Thrombotic Diseases

目的研究我国人群血小板膜糖蛋白(GP)和血管性血友病因子(vWF)基因多态性的分布频率及其与血栓性疾病的关系。方法多态性分布频率的确定采用聚合酶链反应-限制性片段长度多态性技术(PCR-RFLP),多态性与血栓性疾病的关系的调查采用病例-对照研究。结果①我国人群GPIb α中HPA-2a和HPA-2b的杂合率为4.5％,R/S多态性两等位基因的比值为0.486∶0.514,在我国汉彝傣三个民族的人群中,GPIb α基因内可变数目串联重复序列(VNTR)只出现一次重复(D)和二次重复(C)两种等位基因,而且VNTR多态性不是中国汉族人群易患脑血栓(AIS)的危险因素;②GPIa基因内C807T多态性的杂合率为41％,807T纯合子在AIS组与对照组之间差异显著(P<0.01,OR=11.0),尤其在≤60岁的AIS患者与对照组之间的差异更明显(P<0.001,OR=17.8);③中国汉族人及彝族、傣族人vWF基因均有Sma Ⅰ多态性位点,其杂合率分别为49％、47％和46％。汉族人群VNTR和G2805A多态性的杂合率分别为79.4％和39％。其中Sam Ⅰ多态性还可能与脑梗死的发生有关,CC纯合子使患脑梗的危险度提高了3.29倍(OR=3.29,95％CI:1.54～7.01,0.01>P>0.001)。结论我国人群血小板GP和vWF基因多态性具有自己的特点,其中GPIa 807T和vWF Sma Ⅰ多态性可能与我国汉族人群AIS的发生有关。

Objective To investigate the polymorphism frequency in the genes of platelet glycoproteins (GP) and von Willebrand' s factor (vWF) , and its relevance to thrombotic diseases. Methods The different genotypes between the normal controls and patients with thrombotic diseases were identified by using polymerase chain reaction and restriction fragment length polymorphism (PCR - RFIP), and their relationship were performed with case - control study. Results (1)In GPIb gene, the heterozygosity of the HPA - 2a/2b polymorphism was 4.5% , and the R/S allele ratio was 0.486:0.514.The VNTR polymorphism was not different in Han, Yi and Dai populations, which was only found one repeat and two repeats.Besides, the VNTR polymorphism may not be an inherited risk factor for the development of stroke in Chinese population.(2)In GPIa gene, the heterozygosity of C807T polymorphism was 41 %, and the frequency of 807T homozygote was higher in patients with acute is-chemic stroke (AIS) than those in controls (OR=11.0, 95%CI:1.4-88.5, P<0.01), especially in younger patients with their ages lower than 60 (P< 0.001) .(3)In vWF gene, the heterozygosities of the VNTR and G2805A polymorphisms were 79.4% and 39% respectively, and those of the Sma I polymorphism were 49%, 47% and 46% in Han, Yi and Dai populations, respectively. In addition, the prevalence of the CC genotype of the Sma I polymorphism in patients with AIS was significantly increased in comparison with that of the controls (OR= 3.29, 95% CI: 1.54-7.01, 0.01 > P>0.001) . Conclusions The polymorphism prevalence of platelet GP gene and vWF gene in Chinese populations was different from those observed in other populations, and the polymorphisms of the C807T in GPIa gene and the Sma I in vWF gene might be associated with the occurrence of AIS in Chinese Han population.