低密度脂蛋白相关受体蛋白6基因多态性与非酒精性脂肪性肝病发病关系研究

Relationship between low-density lipoprotein receptor-related protein 6 gene polymorphism and occurrence of nonalcoholic fatty liver disease

目的:探究低密度脂蛋白相关受体蛋白6(LRP6)基因多态性与非酒精性脂肪性肝病(NAFLD)发病的关系。方法:选取NAFLD患者(NAFLD组)144例和体检健康者(对照组)135例为研究对象。检测两组血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、三酰甘油(TG)、总胆固醇(TC)、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B(ApoB)以及ApoA1水平;提取两组血清中基因组DNA,采用PCR法扩增LRP6基因rs2302685片段并测序;比较两组一般资料和生化指标;观察两组LRP6基因rs2302685位点基因型分布并进行Hardy-Weinberg(H-W)遗传平衡检验;比较不同LRP6基因型NAFLD患者生化指标;采用Logistic回归分析LRP6基因型对NAFLD发生的影响。结果:与对照组比较,NAFLD组体重指数(BMI)及ALT、TG、LDL-C、ApoB水平升高(均P<0.05)。对照组和NAFLD组LRP6基因在rs2302685位点上均检出TT型、TC型、CC型3种基因型,其中对照组TT基因型最多(57.78%),NAFLD组CC基因型最多(56.94%),对照组与NAFLD组基因型比较差异有统计学意义(P<0.05)。经吻合度检验,对照组和NAFLD组基因多态性分布符合H-W平衡法则(均P>0.05)。TT型、TC型、CC型NAFLD患者BMI、ALT、TG、LDL-C、ApoB水平依次升高(均P<0.05)。CC基因型是影响NAFLD发生的独立危险因素(P<0.05)。结论:LRP6基因多态性与NAFLD有关,其中CC基因型是影响NAFLD发生的独立危险因素。

Objective:To explore the relationship between low-density lipoprotein receptor-related protein 6(LRP6)gene polymorphism and occurrence of nonalcoholic fatty liver disease(NAFLD).Methods:A total of 144 patients with NAFLD(NAFLD group)and 135 healthy subjects(control group)were selected.Automatic biochemical analyzer was used to detect the levels of ALT,AST,TG,TC,LDL-C,HDL-C,apolipoprotein B(ApoB)and ApoA1.Genomic DNA was extracted from serum,the rs2302685 fragment of LRP6 gene was amplified by PCR and sequenced.General data,biochemical indexes,genotype distribution of rs2302685 polymorphism of LRP6 gene and Hardy-Weinberg(H-W)genetic balance test were performed.Biochemical indexes of NAFLD patients with different LRP6 genotypes were compared.Logistic regression was used to analyze the influence of LRP6 genotype on the occurrence of NAFLD.Results:Compared with control group,BMI,ALT,TG,LDL-C and ApoB levels were increased in the NAFLD group(all P<0.05).Three genotypes of TT type,TC type and CC type of the LRP6 gene were detected at the rs2302685 locus of the two groups,and among them,the control group had the most TT genotype(57.78%),and the NAFLD group had the most CC genotype(56.94%),there was statistically significant difference in genotype between the control group and the NAFLD group(P<0.05).After the degree of coincidence test,the distribution of gene polymorphisms in the control group and NAFLD group conformed to the H-W equilibrium law(all P>0.05).The levels of BMI,ALT,TG,LDL-C and ApoB in patients with TT type,TC type and CC type NAFLD were increased successively(all P<0.05).CC genotype was an independent risk factor affecting the occurrence of NAFLD(P<0.05).Conclusion:LRP6 gene polymorphism is related to NAFLD,and CC genotype is an independent risk factor affecting occurrence of NAFLD.