非酒精性脂肪性肝炎患者外周血跨膜蛋白6超家族成员2基因表达与心血管疾病的关系*

doi:10.3969/j.issn.1672-5069.2021.04.013

摘要/Abstract

摘要： 目的探究非酒精性脂肪性肝炎(NASH)患者跨膜蛋白6超家族成员2(TM6SF2)基因表达与心血管疾病(CVD)的关系。方法 2018年9月～2020年9月我院收治的93例NASH患者,根据其是否合并CVD分为NASH组及CVD组,应用TaqMan探针法检测两组患者的TM6SF2基因rs58542936位点多态性,采用Logistic多因素回归分析心血管疾病发生险因素,采用ROC曲线分析TM6SF2基因rs58542936位点多态性对NASH出现CVD的预测价值;根据合并CVD患者TM6SF2基因rs58542936位点多态性将其分为纯合型及杂合型,比较两组患者血脂水平及心功能指标。结果 CVD组在BMI≥28kg/m²、TC≥5.2mmol/L、吸烟、有心血管疾病家族史及TM6SF2基因rs58542936位点为杂合型的人数比例分别为51.4%、82.9%、57.1%、51.4%、40.0%,大于NASH组(29.3%、63.8%、31.0%、27.6%、20.7%,P<0.05);经多元logistics回归分析,BMI≥28kg/m²[OR(95%CI)为1.7(1.0～2.8)]、TC≥5.2mmol/L[OR(95%CI)为1.8(1.1～3.1)]、有心血管疾病家族史[OR(95%CI)为1.8(1.1～2.9)]及TM6SF2基因rs58542936位点CT型[OR(95%CI)为1.8(1.1～3.0)]是影响CVD发生的危险因素(P<0.05);TM6SF2基因rs58542936位点多态性预测NASH出现CVD的AUC为0.7;TM6SF2基因rs58542936位点杂合型TC、TG水平及LVEF、IMT值分别为(6.3±1.0)mmol/L、(2.0±0.4)mmol/L、(56.1±2.9)%、(1.3±0.2)mm,高于或大于纯合型的[(5.0±0.9)mmol/L、(1.6±0.3)mmol/L、(57.9±2.9)%、(0.9±0.2)mm,P<0.05]。结论 TM6SF2基因rs58542936位点多态性是影响NASH出现CVD的危险因素,且对CVD的出现具有预测价值,TM6SF2基因rs58542936位点杂合型患者存在心功能较差的现象。

关键词: 非酒精性脂肪性肝炎, 跨膜蛋白6超家族成员2, 心血管疾病

Abstract: Objective To explore the relationship between the expression of transmembrane 6 superfamily member 2 (TM6SF2) gene and cardiovascular disease (CVD) in patients with non-alcoholic steatohepatitis (NASH). Methods A total of 93 NASH patients who were admitted to the hospital from September 2018 to September 2020 were enrolled. According to presence or absence of CVD, they were divided into NASH group and CVD group. The polymorphism of TM6SF2 gene at rs58542936 locus was detected by TaqMan probe method. The influencing factors of CVD were analyzed by Logistic multivariate regression analysis. The predictive value of TM6SF2 gene polymorphism at rs58542936 locus for CVD was analyzed by ROC curves. According to the polymorphism of TM6SF2 gene at rs58542936 locus in CVD patients, they were divided into homozygous group and heterozygous group. The levels of blood lipid and cardiac function indexes were compared betweenthe two groups. Results The proportions of cases with BMI not lower than 28kg/m², TC not lower than 5.2 mmol/L, smoking history, family history of CVD and heterozygous TM6SF2 gene at rs58542936 locus in CVD group were 51.4%, 82.9%, 57.1%, 51.4% and 40.0%, higher than those in NASH group (29.3%, 63.8%, 31.0%, 27.6%, 20.7%, P<0.05). The multivariate Logistics regression analysis showed that BMI not lower than 28 kg/m² [OR(95%CI): 1.7 (1.0-2.8)], TC not lower than 5.2 mmol/L [OR(95%CI): 1.8 (1.1-3.1)], family history of CVD [OR (95%CI): 1.8 (1.1-2.9)] and CT type TM6SF2 gene at rs58542936 locus [OR (95%CI): 1.8 (1.1-3.0)] were risk factors of CVD (P<0.05). AUC of TM6SF2 gene polymorphism at rs58542936 locus for predicting CVD was 0.7. TC, TG, LVEF and IMT in heterozygous TM6SF2 gene at rs58542936 locus were (6.3±1.0) mmol/L, (2.0±0.4) mmol/L, (56.1±2.9) % and (1.3±0.2) mm, higher or greater than those in homozygous type [(5.0±0.9) mmol/L, (1.6±0.3) mmol/L,(57.9±2.9) %, (0.9±0.2) mm] (P<0.05). Conclusion The polymorphism of TM6SF2 gene at rs58542936 locus is a risk factor of CVD, which is of predictive value for the occurrence of CVD. The cardiac function is worse in patients with heterozygous TM6SF2 gene at rs58542936 locus.

Key words: Non-alcoholic steatohepatitis, Transmembrane 6 superfamily member 2, Cardiovascular disease

吴丽蒙, 龚翔, 张燕. 非酒精性脂肪性肝炎患者外周血跨膜蛋白6超家族成员2基因表达与心血管疾病的关系^*[J]. 实用肝脏病杂志, 2021, 24(4): 504-507.

Wu limeng, Gong Xiang, Zhang Yan. Relationship between the expression of transmembrane 6 superfamily member 2 gene and cardiovascular disease in patients with non-alcoholic steatohepatitis[J]. Journal of Practical Hepatology, 2021, 24(4): 504-507.

参考文献

[1] Sookoian S, Castao GO, Scian R, et al. Genetic variation in transmembrane 6 superfamily member 2 and the risk of nonalcoholic fatty liver disease and histological disease severity. Hepatology, 2015, 61(2):515-525.
[2] Pang J, Xu W, Zhang X, et al. Significant positive association of endotoxemia with histological severity in 237 patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther, 2017, 46(2):175-182.
[3] Enea B, Claudio C, Paolo V, et al. Association of nonalcoholic fatty liver disease with subclinical cardiovascular changes: a systematic review and meta-analysis. Biomed Res Int, 2015, 15(5):1-11.
[4] 中华医学会肝病学分会脂肪肝和酒精性肝病学组, 中国医师协会脂肪性肝病专家委员会.非酒精性脂肪性肝病防治指南(2018年更新版). 实用肝脏病杂志, 2018, 21(2):177-186.
[5] 何伋. 实用临床心脑血管病学. 吉林:吉林科学技术出版社,2014:12-13.
[6] Dongiovanni P, Petta S, Maglio C, et al. Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology, 2015, 61(2):506-514.
[7] 毛重山, 殷辉, 肖二辉, 等. 非诺贝特对非酒精性脂肪性肝病合并2型糖尿病患者血脂,血管内皮功能和肝纤维化指标的影响. 实用肝脏病杂志, 2020, 23(1):50-53.
[8] Milano M, Aghemo A, Mancina RM, et al. Transmembrane 6 superfamily member 2 gene E167K variant impacts on steatosis and liver damage in chronic hepatitis C patients. Hepatology, 2015, 62(1):111-117.
[9] Kim D, Kim W, Joo SK, et al. Association between body size-metabolic phenotype and nonalcoholic steatohepatitis and significant fibrosis. J Gastroenterol, 2020, 55(3):330-341.
[10] Stefan N, Häring HU, Cusi K, et al. Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies.Lancet Diabetes Endocrinol, 2019, 7(4):313-324.
[11] Ludovica FA, Giuseppina P, Dario C, et al. Epicardial adipose tissue (EAT) thickness is associated with cardiovascular and liver damage in nonalcoholic fatty liver disease. PLoS One, 2016, 11(9):162473.
[12] Pirola CJ, Sookoian S. The dual and opposite role of the TM6SF2-rs58542926 variant in protecting against cardiovascular disease and conferring risk for nonalcoholic fatty liver: a meta-analysis. Hepatology, 2016, 62(6):1742-1756.
[13] 沈剑华, 张爽, 李异玲. 中国汉族人群跨膜蛋白6超家族成员2 rs58542926基因多态性与肝硬化的相关性. 中华消化杂志, 2017, 37(8):550-554.
[14] Kahali B,Liu YL, Daly AK, et al. TM6SF2: catch-22 in the fight against nonalcoholic fatty liver disease and cardiovascular disease. Gastroenterology, 2015, 148(4):679-684.
[15] 王立芹, 郭维恒, 郭志旺, 等. PNPLA3,TM6SF2基因多态性及其与吸烟,饮酒交互作用对HBV相关肝癌的影响. 中华流行病学杂志, 2018, 39(12):1611-1616.
[16] Feldman A, Eder SK, Felder TK, et al. TM6SF2 andncan wildtype together with several long-chain phosphatidylcholines are linked to a healthy liver in obese subjects. J Hepatology, 2016, 64(2):183-186.
[17] Eslam M, Mangia A, Berg T, et al. Diverse impacts of the rs58542926 E167K variant in TM6SF2 on viral and metabolic liver disease phenotypes. Hepatology, 2016, 64(1):34-46.
[18] Musso G, Cipolla U, Cassader M, et al. TM6SF2 rs58542926 variant affects postprandial lipoprotein metabolism and glucosehomeostasis in nafld. J Lipid Res, 2017, 58(6):1221-1229.

非酒精性脂肪性肝炎患者外周血跨膜蛋白6超家族成员2基因表达与心血管疾病的关系^*

Relationship between the expression of transmembrane 6 superfamily member 2 gene and cardiovascular disease in patients with non-alcoholic steatohepatitis

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