高胆固醇血症患者LDL—R基因第4外显子XspI位点多态性与血清Hs-CRP的关系及意义

目的探讨高胆固醇血症患者低密度脂蛋白受体（LDL．R）基因第4外显子XspI住点多态性与血清超敏C反应蛋白（Hs-CRP）的关系及意义。方法用聚合酶链反应一限制性片段长度多态性（PCR—RFLP）技术结合DNA测序技术检测1250例高胆固醇血症患者和1200例健康体检者LDL．R基因第4外显子的XspI酶切位点多态性；按基因型分组，用动态定时散射比浊法检测各基因型Hs—CRP的浓度，对两者关系进行分析；同时检测各组的血脂指标。结果与健康对照组比较，高胆固醇血症组血清Hs-CRP明显升高，HDL-C降低（P均〈0．05）；根据LDL—R第4外显子处是否有XspI酶切位点，分为X＋X＋、X＋X-、X-X-3种基因型，X-X-组、X＋X-组、X＋X＋组血清Hs—CRP水平依次升高（P均〈0．05）；多元线性回归分析显示，基因型和胆固醇水平是Hs—CRP水平的独立影响因素。结论高胆固醇血症患者血清Hs-CRP水平升高，LDL-R基因X＋X＋基因型Hs—CRP水平升高，LDL-R基因第4外显子的XspI位点多态性可能通过影响Hs-CRP水平促进高胆固醇血症。

Relationship between XspI site polymorphism of LDL-R gene and serum Hs-CRP in patients with hypercholesterolemia

Objective To investigate the correlation between Xsp I site polymorphism of exon 4 in low-density lipoprotein receptor （LDL-R） gene and serum high-sensitive C-reactive protein （Hs-CRP） levels in patients with hypercholesterolemia and its significance. Methods Xsp I site polymorphism of exon 4 in LDL-R gene was detected by PCR-RFLP and DNA sequencing in 1,250 patients with hypercholesterolemia and 1,200 healthy subjects. All the subjects were divided into three groups according to the genotypes of XspI site ： X ＋ X ＋ group, X ＋ X - group and X - X - group. The levels of serum Hs-CRP were detected by Vlin-Integral Nephelometry. The levels of serum lipids were detected simultaneously. The relationship between Hs-CRP levels and genotype of XspI was analyzed. Results The serum levels of Hs-CRP in patients were significantly higher than those of healthy subjects, however, the levels of HDL-c were significantly lower than those of controls （ P 〈 0.05 ）. The level of Hs-CRP were increased in the order of genotype X - X - , X ＋ X - and X ＋ X＋, with statistical significance among the three groups （ P 〈 0.05 ）. Stepwise multiple linear regression analysis showed that total cholesterol affected the levels of serum Hs-CRP, and the genotype X ＋ X＋ of XspI site was the independent factor of affecting serum Hs-CRP levels. Conclusion The serum levels of Hs-CRP are increased in patients with hypercholesterolemia, so are in X ＋X ＋ of LDL-R gene, moreover,Xsp I site polymorphism of exon 4 in LDL-R gene can aggravate hypercholesterolemia by affecting the levels of Hs-CRP.