非酒精性脂肪性肝病患者载脂蛋白B基因单核苷酸多态性的基因芯片研究

Relation between apolipoprotein B gene SNPs and nonalcoholic fatty liver disease studied by the technique of oligonucleotide arrays

目的探讨ApoB MspⅠ、XbaⅠ、EcoRⅠ位点单核苷酸多态性与非酒精性脂肪肝(NAFLD)发病及血清脂质代谢的关系。方法应用PCR反应和基因芯片杂交技术,对非酒精性脂肪性肝病患者(NAFLD组,299例)和健康人群(对照组,278例)的ApoB MspⅠ、XbaⅠ、EcoRⅠ位点的多态性进行分析。结果 NAFLD组MspⅠ和XbaⅠ位点少见等位基因频率(M-和X+)分别为0.065和0.062,高于对照组的0.038和0.031,差异有统计学意义。ApoB MspⅠ位点M+M-与M+M+的HDL-C和LDL-C水平差异有统计学意义,而XbaⅠ位点不同基因型之间的血脂、载脂蛋白水平的差异无统计学意义。结论 ApoB MspⅠ、XbaⅠ位点多态性与NAFLD的发病相关,ApoB MspⅠ、XbaⅠ位点可能为NAFLD的易感基因。

Objective To study the relationship between the apolilpoprotein B gene polymorphisms and serum lipids me- tabolism in patients of nonalcoholic fatty liver disease. Methods The SNPs at Msp I . Xba I . EcoR I site of the apolilpopro- tein 3 （Apo3） gene was studied using the technique of PCR and oligonucleotide arrays in a sample of 278 healthy individuals and 299 patients with nonalcoholic fatty liver disease. Results The frequency of the rarer allele M- of the Msp I site and the rarer allele X＋ allele of the EcoR I site was significantly higher among patients （0. 065 and 0. 062, respectively） than among controls （0. 038 and 0. 031 respectively）. In the Msp I polymorphism, LDL-C and HDL-C levels of the M＋ M- genotype were signifi- cantly higher than those of the others. The other lipid and apolipoprotein levels were not different significantly among the three genotypes. In the Xba I polymorphism, there were no significant differences in serum lipids and lipoproteins among the three genotypes. Conclusion These findings indicate that ApoB gene Msp I . Xba I site SNPs are associated with the occurrence of nonalcoholic fatty liver disease and that variation at Msp I of the ApoB gene is involved in the regulation of LDL-C and HDL-C metabolism.