胆囊结石病家系的基因多态性研究

Study of susceptible gene polymorphism in pedigrees of cholelithiasis

目的 从胆囊结石病多发家系角度来探讨胆石症发病的分子基础并研究部分胆石病易感基因在胆石病家系成员中的分布及与胆石病的关系。方法 收集调查上海地区93个胆石病家系,通过胆囊B超检查证实每个家系至少有2名胆石病患者,对333名家系成员（其中患者239人）进行临床调查并检测血脂水平,应用 PCR-RFLP（PCR-限制性多形性碎片长度）法来检测胆石病易感基因载脂蛋白 B（Apo B）基因Xbal和载脂蛋白E（Apo E）基因Hha I的多态性位点基因型,分析各基因型和等位基因在家系成员中的分布情况。结果 （1）Apo B基因 Xba I多态性 X+/-基因型频率在胆石组为5.9％,非胆石组为10.6％,分布无显著性差异。不同的Apo B基因型,其血液生化指标无显著性差异。（2）Apo E基因多态性各等位基因ε2、ε3和ε4的分布频率在胆石组分别为:6.9％、81.4％和11.7％,在非胆石组分别为:9.0％、81.4％和9.6％,分布无显著性差异。年龄段为≤40岁的家系成员中,Apo E4/x（Apo E3/4,Apo E4/4）基因型在胆石组的分布频率（20.6％）显著高于非胆石组（0％）（P=0.04）。不同的Apo E基因型对血脂水平有着不同的影响,总体上看,E2/x（Apo E2/2,Apo E2/3）基因型者的血清TG和HDLC显著升高,LDLC显著降低（P<0.05）;而E4/x基因型者的TC、LDLC。

Objective To explore the molecular mechanism of cholelithiasis through the pedigrees and study the distribution of susceptible gene polymorphisms in pedigrees. Methods Ninety - three pedigrees of cholelithiasis were investigated in Shanghai. Each pedigree contained more than two patients of cholelithiasis which were proved by B - type ultrasonograghy. Clinical investigations and Serum lipids assay were made in 333 subjects including 239 patients and 94 cases of control. Genotypes of the Xba I polymorphism of Apo B gene and Hha I polymorphism of Apo E gene were determined by PCR- RFLP. The frequencies of genotypes and alleles were compared between patients and normal subjects. Results (1)The frequency of X+ allele was 5.9% in patients and 10.6% in normal subjects and there was no significant difference in distribution. The serum examination showed no significant difference between different genotype. (2) The distribution frequencies of ε2, ε3 and ε4 alleles in Apo E gene were 6.9% , 81.4% and 11.7% respectively in patients; 9.0% , 81.4% and 9.6% respectively in controls. There was no significant difference between the two groups. In the subjects younger than 40 years old, frequency of Apo E4/x (E3/4 and E4/4) genotypes in patients was significantly higher than that in controls (20.6% vs 0% , P =0.04). Different Apo E genotypes took different effects on serum levels of lipids. Generally speaking, levels of serum TG and HDLC were significantly higher while LDLC was lower in E2/x (E2/2 and E2/3) genotypes ( P < 0.05) ; levels of serum of TC, LDLC, Apo B and Apo E were higher while HDLC and Apo A, were lower in E4/x genotypes(P < 0.05) . Conclusions ε4 allele of Apo E gene may be susceptible gene of cholelithiasis. Relationship between X+ allele of Apo B gene and cholelithiasis needs more studies.