低密度脂蛋白受体基因I334V突变与高胆固醇血症的相关性

Relationships between I334V Mutation of LDL Receptor Gene and Hypercholesterolemia

目的通过检测低密度脂蛋白受体(LDL-R)基因第8外显子I334V突变,分析LDL-R基因多态性与高胆固醇血症的关系及意义。方法应用PCR-RFLP技术,根据限制性内切酶ClaⅠ酶切位点存在与否,分为Ⅱ、Ⅳ、VV3种基因型和I、V两种等位基因。共对620例高胆固醇血症、420例边缘高胆固醇血症及350例正常血脂人群(正常对照组)LDL-R基因第8外显子I334V突变的多态性进行了检测。结果 (1)与正常对照组比较,高胆固醇血症组、边缘高胆固醇血症组低密度脂蛋白胆固醇(LDL-C)水平显著升高,高密度脂蛋白胆固醇(HDL-C)水平显著降低(P均<0.05)。(2)高胆固醇血症组的VV基因型频率及V等位基因频率显著高于边缘高胆固醇血症组及正常对照组(P均<0.01)。(3)Ⅱ、Ⅳ、VV基因型的受检者总胆固醇(TC)、LDL-C水平逐步升高,HDL-C水平逐步下降(P均<0.05)。(4)Logistic回归分析显示,LDL-R基因VV基因型是高胆固醇血症的危险因素,HDL-C是高胆固醇血症的保护性因素(P均<0.05)。结论 LDL-R基因第8外显子I334V位点存在基因多态性表达,该位点突变与高胆固醇血症有关。

Objective To study the relationships between I334V mutation in exon 8 of low density lipoprotein receptor （ LDL - R） gene and hypercholesterolemia. Methods PCR - RFLP assay was applied to discriminate the three genotypes of II, IV, and VV, as well as the two alleles of I and V, according to the existing status of a Cla I site. I334V mutation in exon 8 of LDL - R gene in 620 cases of hypercholesterolemia, 420 borderline hypercholesterolemia patients, and 350 normal control subjects were determined. Results The hypereholesterolemia group and the borderline hypereholesterolemia group showed significant- ly higher serum levels of LDL - C and lower levels of HDL - C than the control group （ P 〈 0.05 ） . The hypercholesterolemia group showed significantly higher frequency of VV genotype and allele V than the borderline hypereholesterolemia group and the control group （ P 〈 0. 01 ） . Comparison among genotypes showed gradually increased serum TC and LDL - C levels and gradually decreased HDL - C levels from 1I to IV, and further, to VV （ P 〈 0. 05） . Logistic regressive analysis showed that VV genotypeof LDL - R gene was among the risk factor of hypercholesterolemia, and the HDL - C was the protective factor. Conclusion The existence of polymorphism in exon 8 of LDL - R gene is with a risk factor for hypercholesterolemia.