P47phox基因第4外显子多态性与湖南省汉族人群脑梗死的相关研究

Relationship between polymorphisms of p47phox gene exon 4 and cerebral infarction in Hunan Han population

摘要:

目的 探讨P47phox基因第4外显子G338A（Arg90His）和G457A（Thr129Thr）多态性与湖南省汉族人群脑梗死的相关性。方法 采用PCR-单链构象多态技术和DNA直接测序法检测湖南省汉族人群散发性脑梗死患者110例、10个脑梗死家系成员110例及100例健康对照组的P47phox基因第4外显子G338A和G457A多态性。酶法测定总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C），免疫比浊法测定apoA-I及apoB100，ELISA法测定Lp（a）血清水平。结果 p47phox基因第4外显子G338A多态存在GG、GA和AA 3种基因型，脑梗死组及其各亚型组G338A多态A等位基因频率分布与对照组比较，差异均有统计学意义（P <0.01）；G457A多态存在GG和GA两种基因型，脑梗死组及其各亚型组G457A多态基因频率分布与对照组比较，差异无统计学意义（P >0.05）；脑梗死组及其各亚型组血清TC、TG、LDL-c及Lp（a）水平明显高于对照组，差异有统计学意义（P <0.01）；组内不同基因型间血脂、脂蛋白水平与对照组比较，差异无统计学意义（P >0.05）。结论 p47phox基因G338A多态A等位基因可能是脑梗死，特别是有高血压病性和糖尿病性脑梗死患者的一个危险因素；G457A多态可能与脑梗死的发病无关。p47phox基因G338A和G457A多态性与血脂代谢可能有关。

Abstract:

【Objective】 To investigate the relationship between polymorphisms of G338A (Arg90His) and G457A (Thr129Thr) of p47phox gene exon 4 and cerebral infarction(CI) in Hunan Han population. 【Methods】 The G338A and G457A polymorphisms of p47phox gene exon 4 in 110 patients with cerebral infarction (CI), 100 sex- and age-matched healthy controls and 10 CI pedigrees from Hunan Han population were determined by PCR-single strand conformation polymorphism analysis and DNA sequencing. TC, TG, HDL-C and LDL-C levels were tested using enzymatic method; apoA-I and apoB100 were measured with immunoturbidimetry; and plasma lipoprotein (a) [Lp(a)] level was measured by ELISA. 【Results】 Three gene types GG, GA and AA were found in the G338A polymorphism site of p47phox gene exon 4. Statistically significant differences were found in the frequencies of A allele of G338A polymorphism between the CI groups and the control group (P < 0.01). Two gene types GG and GA were found in the G457A polymorphism site of p47phox gene exon 4. No statistically significant differences were found in the frequencies of genotypes and alleles of G457A polymorphism between the CI groups and the control group (P > 0.05). The serum levels of TC, TG, LDL-C and Lp(a) of the CI groups were markedly higher than those of the control group (P < 0.01). 【Conclusions】 An allele in G338A polymorphism of p47phox gene exon 4 may be one of the risk factors of CI patients, especially the CI patients accompanied with hypertension or diabetes. The gene G457A is probably not related with the onset of CI. The G338A and G457A polymorphisms of p47phox gene are probably associated with plasma lipid metabolism.