载脂蛋白B基因单核苷酸多态性与非酒精性脂肪性肝病

Relationship between single nucleotide polymorphism of apolipoprotein B gene and nonalcoholic fatty liver disease

目的:探讨载脂蛋白(ApoB)MspⅠ,XbaⅠ,EcoRⅠ位点单核苷酸多态性(SNP)与非酒精性脂肪性肝病(NAFLD)发病的关系,以及其对血清脂质代谢的影响.方法:应用聚合酶链反应和寡核苷酸芯片杂交技术,对299例非酒精性脂肪性肝病患者和278例正常对照的ApoBMspⅠ,XbaⅠ,EcoRⅠ位点的多态性进行分析,同时检测其血清样本总胆固醇(TC),甘油三酯(TG),低密度脂蛋白胆固醇(LDL-C),高密度脂蛋白胆固醇(HDL-C),载脂蛋白AⅠ(ApoAⅠ)和载脂蛋白B(ApoB)含量.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,差别有统计学意义(P<0.05);ApoBEcoRⅠ位点少见等位基因E+在两组间的分布无差别.ApoBMspⅠ位点M+M-基因型者HDL-C和LDL-C水平明显高于M+M+者(分别为1.75±0.25vs1.62±0.30,P<0.05;3.00±0.62vs2.79±0.78,P<0.05),而XbaⅠ位点不同基因型之间的血脂、载脂蛋白水平差别无统计学意义.结论:NAFLD的发病与ApoBMspⅠ,XbaⅠ位点多态性有关联,ApoBMspⅠ,XbaⅠ位点可能为NAFLD的易感基因.

AIM： To investigate the relations of single nucleotide polymorphism （SNP） of the apolipoprotein B （ApoB） gene at Msp Ⅰ, Xba Ⅰ and EcoR Ⅰ sites with the pathogenesis of nonalcoholic fatty liver disease （NAFLD）. METHODS： The SNP of ApoB gene at MspⅠ, Xba Ⅰ and EcoR Ⅰ sites was analyzed using polymerase chain reaction and oligonucleotide arrays in 299 patients with NAFLD and 278 healthy controls. Total cholesterol （TC）, triglycerides （TG）, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C）, ApoB and ApoA Ⅰ were also detected in the blood samples from those patients and controls. RESULTS： The frequencies of the rare allele M at MspⅠ site and X^＋ at Xba Ⅰ sites were significantly higher in NAFLD patients than those in the controls （M： 0.065 vs 0.038, P 〈0.05; X^＋： 0.062 vs 0.031, P 〈0.05）. The rare allele at EcoR ~ site was not notably different between the patients and controls. In the Msp Ⅰ polymorphism, The HDL-C and LDL-C levels of patients with M^＋M^- genotype at msp Ⅰ site were markedly higher than those with M^＋M^- genotype （1.75±0.25 vs 1.62±0.30, P 〈0.05; 3.00±0.62 vs 2.79±0.78, P 〈0.05）. The levels of blood lipid and apolipoprotein were not significantly different between patients with different genotypes at Xba Ⅰ site. CONCLUSION： The ApoB SNP at Msp Ⅰ and Xba Ⅰ sites is involved in the pathogenesis of NAFLD, and the variation at MspⅠ site is associated with the regulation of LDL-C and HDL-C metabolism.