FgBβ基因多态性与其功能表达和肥胖的相关性研究

目的 研究体重超重和肥胖与纤维蛋白原(Fg) Bβ链基因多态性以及血浆Fg功能表达的关系,探讨其发生脑梗死等相关疾病的发病机制.方法 选取开滦集团离退休职工939人进行体检和问卷调查,依体重指数将其分为体重正常、超重及肥胖三组,受检者均抽取静脉血测定血液生化及血浆Fg浓度和纤维蛋白单体聚合反应速率(FMPV)、FMPV/Amax等反映Fg分子聚合功能的指标,并应用聚合酶链反应-限制性内切酶片段长度多态性等技术进行FgBβ链七位点基因多态性检测.结果 三组间七个位点的等位基因和基因型的频率分布均无统计学差异(P＞0.05);肥胖组Bβ-993位点突变基因型人群Fg浓度、FMPV、Amax均高于野生基因型人群,βI6和345位点突变基因型人群Amax也高于野生基因型(P＜0.05);超重组和肥胖组的高血压病、脑梗死发病率均高于正常体重组(P＜0.05);以体重指数为因变量进行多元逐步回归分析,依次筛选出高血压病、年龄、脑梗死病史(P＜0.01),结论 在正常体重和超重状态下FgBβ上述7位点基因多态性不影响血浆Fg浓度和功能的表达,而肥胖状态可使FgBβI6、-993和345变异基因型携带者的血浆Fg浓度和综合性纤维蛋白聚合功能明显升高,成为发生血栓性疾病的重要病因,提示体重超重与肥胖状态发生脑梗死等血栓性疾病的危险性和发病机制不同.

Analysis on the correlation of beta-fibrinogen gene polymorphisms and its functional expression with obesity

Objective To study the correlation of overweight, obesity and beta-fibrinogen（Fg） gene polymorphisms with fibrinogen functional expression such as plasma fibrinogen concentration and molecular reactivity. Methods 939 subjects of retired employees from Kailuan corporation were enrolled with medical） examination and questionnaire survey. Subjects were divided into normal weight group, overweight group, obese group based on body mass index. Blood biochemistry, plasma fibrinogen concentration, fibrin monomer polymerized velocity （FMPV）, absorbance maximum （Amax） and FMPV/Amax were measured in all subjects. The gene polymorphisms at seven sites of Fg β-chain were detected by polymerase chain reaction-restriction fragment length polymorphism and gene sequencing. Results The genotype and allele frequencies of the seven sites were not significantly different among the three groups （ P 〉 0. 05） ; In obese group, Fg concentration, FMPV, FMPV/Amax with β-993 mutated genotype were significantly higher than those with wild genotype （ P 〈 0. 05 ）, Amax with 1316 and β345 mutated genotypes were higher than those with wild genotype in obese group （ P 〈 0. 05 ）. The incidence of hypertention and cerebral Infarction in overweight and obese groups were higher than that in normal . weight group（ P 〈 0.05 ）. In multiple stepwise regression analysis with body mass index as the dependent variable, hypertension, age and cerebral infarction were selected （ P 〈 0. 01 ）. Conclusion The beta-fibrinogengene polymorphisms do not affect Fg concentration and molecular reactivity in normal weight and overweight status. Obese individuals with β16, β-993 and 345 mutated genotypes may have higher levels of plasma fibrinogen concentration and molecular reactivity. Therefore, the latter status associates with the incidence of cerebral infarction and other thrombosis diseases.