机构地区:[1]首都医科大学附属北京佑安医院肝病中心三科,北京100069 [2]北京肝病研究所,北京100069 [3]首都体育学院,北京100191
出 处:《临床肝胆病杂志》2023年第3期552-561,共10页Journal of Clinical Hepatology
基 金:北京市百千万人才工程资助项目(2019A15);北京市属医学科研院所公益发展改革试点项目(京医研2021-10)。
摘 要:目的探讨老年人群微粒体甘油三酯转运蛋白(MTTP)基因rs1800591多态性与非酒精性脂肪性肝病(NAFLD)发病风险的关系。方法本研究的临床队列建立在北京京煤集团总医院门矿医院,2020年1月11日—2021年9月30日在北京门头沟社区共招募参加健康体检1098例老年志愿者,其中NAFLD患者614例,非NAFLD患者484例,采用基因芯片法检测MTTP rs1800591基因型,收集人口学资料并检测受试者的血液生化指标。符合正态分布的计量资料两组间比较采用独立样本t检验;对非正态分布的计量资料两组间比较采用Mann-Whitney U检验;计数资料两组间比较采用χ^(2)检验。应用χ^(2)检验分析基因型频率的分布是否符合Hardy-Weinberg(H-W)平衡检验以确认样本的群体代表性。以非条件Logistic回归模型计算比值比(OR)及其95%CI以评估基因多态性与NAFLD发生风险及其他合并症的关系。结果两组间性别、年龄差异均有统计学意义(P值均<0.05)。相比于非NAFLD组,NAFLD组的BMI、腰臀比、TG、ALT、AST、CAP、LSM水平均显著提高,而HDL明显降低(P值均<0.05)。NAFLD组中高血压、糖尿病、肥胖及代谢综合征患者的比例也均高于非NAFLD组(P值均<0.05)。MTTP rs1800591多态性在对照组基因型频率分布符合Hardy-Weinberg平衡(χ^(2)=1.097,P=0.29)。MTTP rs1800591不同基因型及等位基因分布在NAFLD患者与对照组中均有显著性差异(P值均<0.001)。总人群中T等位基因(GT+TT,n=351)携带率在男性中比例偏低,而BMI和CAP值显著高于非携带者(GG,n=747)(P值均<0.001)。相比于非携带者,T等位基因携带者(GT+TT,n=232)中肥胖患者比例明显提高,但NFS评分却显著降低(P值均<0.05)。在NAFLD受试者中,T等位基因携带者男性比例和腰臀比显著降低,T等位基因携带者HDL高于非携带者(GG,n=382),T等位基因携带者NFS评分仍明显低于非携带者(P值均<0.05)。非条件Logistic回归分析表明,在校正性别、年龄、BMObjective To investigate the association between the polymorphism of the microsomal triglyceride transport protein(MTTP)gene at rs1800591 locus and the risk of nonalcoholic fatty liver disease(NAFLD)in the elderly population.Methods The clinical cohort of this study was established in Menkuang Hospital,Beijing Jingmei Group General Hospital.A total of 1098 healthy elderly volunteers were recruited for physical examination in communities in Mentougou District of Beijing,China,from January 11,2020 to September 30,2021,among whom there were 614 patients with NAFLD and 484 individuals without NAFLD.Gene microarray was used to determine the genotypes of MTTP rs1800591;demographic data were collected,and blood biochemical parameters were measured.The independent samples t-test was used for comparison of normally distributed continuous data between groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups;the chi-square test was used for comparison of categorical data between groups.The chi-square test was used to investigate whether the distribution of genotype frequency was in accordance with Hardy-Weinberg equilibrium.The unconditional logistic regression model was used to calculate odds ratio(OR)and its 95%confidence interval(CI)to investigate the association of gene polymorphism with the risk of NAFLD and other comorbidities.Results There were significant differences in sex and age between the two groups(P<0.05).Compared with the non-NAFLD group,the NAFLD group had significantly higher levels of body mass index(BMI),waist-hip ratio,triglyceride,alanine aminotransferase,aspartate aminotransferase,controlled attenuation parameter(CAP),and liver stiffness measurement and a significantly lower level of high-density lipoprotein(HDL)(all P<0.05).Compared with the non-NAFLD group,the NAFLD group had a significantly higher proportion of patients with hypertension,diabetes,obesity,and metabolic syndrome(all P<0.05).The distribution of genotype frequency at MTTP rs1
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