微粒体甘油三酯转运蛋白基因...性脂肪性肝病发生风险的关系_赵锦涵.pdf

脂肪性肝病DOI:10 3969/j issn1001 5256 2023 03 011微粒体甘油三酯转运蛋白基因 rs1800591 变异与老年人群非酒精性脂肪性肝病发生风险的关系赵锦涵1，张晶1，张洋2，徐潇艺1，勾钰淞1，徐航飞1，万妍3，吴剑31 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通信作者:吴剑，wujiancupes126 com(OCID:0000 0001 6690 4561)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 2检验。应用 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(O)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(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、BMI 混杂因素后，MTTPrs1800591 GT+TT 型仍显著增加了 NAFLD 的发生风险(O=1 643，95%CI:1 226 2 203，P=0 001)，而 T 等位基因携带则增加了总人群中肥胖的发生风险(O=1 371，95%CI:1 051 1 788，P=0 02)。结论老年人群中 MTTPrs1800591 多态性与 NAFLD 的发生有关，T 等位基因携带者可能促进了 NAFLD 肝脏脂肪变性，增加肥胖症发生风险，但可能抑制了肝纤维化进展。关键词:非酒精性脂肪性肝病;基因;老年人基金项目: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)Association between the rs1800591 variation of the microsomal triglyceride transfer protein gene and the risk ofnonalcoholic fatty liver disease in the elderly populationZHAO Jinhan1，ZHANG Jing1，ZHANG Yang2，XU Xiaoyi1，GOU Yusong1，XU Hangfei1，WAN Yan3，WU Jian3(1 Third Department of Liver Disease Center，Beijing YouAn Hospital，Capital Medical University，Beijing 100069，Chi-255临床肝胆病杂志第39 卷第3 期2023 年3 月J Clin Hepatol，Vol39 No3，Mar2023na;2 Beijing Institute of Hepatology，Beijing 100069，China;3 Capital University of Physical Education and Sports，Beijing 100191，China)Corresponding author:WU Jian，wujiancupes126 com(OCID:0000 0001 6690 4561)Abstract:ObjectiveTo investigate the association between the polymorphism of the microsomal triglyceride transport pro-tein(MTTP)gene at rs1800591 locus and the risk of nonalcoholic fatty liver disease(NAFLD)in the elderly populationMethodsThe clinical cohort of this study was established in Menkuang Hospital，Beijing Jingmei Group General Hospital Atotal of 1098 healthy elderly volunteers were recruited for physical examination in communities in Mentougou District of Bei-jing，China，from January 11，2020 to September 30，2021，among whom there were 614 patients with NAFLD and 484 indi-viduals without NAFLD Gene microarray was used to determine the genotypes of MTTP rs1800591;demographic data werecollected，and blood biochemical parameters were measured The independent samples t test was used for comparison of nor-mally distributed continuous data between groups，and the Mann Whitney U test was used for comparison of non normallydistributed continuous data between groups;the chi square test was used for comparison of categorical data between groupsThe 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(O)and its 95%confi-dence interval(CI)to investigate the association of gene polymorphism with the risk of NAFLD and other comorbiditiesesultsThere 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，al-anine aminotransferase，aspartate aminotransferase，controlled attenuation parameter(CAP)，and liver stiffness measurementand 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 syn-drome(all P 0 05)The distribution of genotype frequency at MTTP rs1800591 locus was in accordance with Hardy Wein-berg equilibrium in the control group(2=1 097，P=0 29)There were a significant differences in the genotype and thedistribution of alleles at MTTP rs1800591 locus between the patients with NAFLD and the control group(all P 0 001)Inthe total population，there was a significantly lower carrying rate of T allele(GT+TT，n=351)in male individuals，and theindividuals carrying T allele had significantly higher BMI and CAP than those carrying GG allele(n=747)(P 0 001)Compared with the individuals who did not carry T allele，the individuals carrying T allele(GT+TT，n=232)had a signifi-cantly higher proportion of patients with obesity and a significantly lower NFS score(P 0 05)As for the individuals