PNPLA3和FABP1基因甲基化与代谢相关脂肪性肝病相关性分析

摘要/Abstract

摘要： 目的了解乌鲁木齐市代谢相关脂肪性肝病(MAFLD)患病率情况及PNPLA3与FABP1基因甲基化对其发病的影响。方法回顾性分析2022年1月—3月新疆医科大学第一附属医院进行体检人群的相关临床资料;从中招募15例MAFLD患者,匹配同期体检15名无肝病既往史健康人群采用甲基化特异PCR方法(MSP法)进行PNPLA3、FABP1基因甲基化检测。采用Point-biserial相关对临床资料及基因表达之间的相关性进行分析。结果共纳入3 194名体检人群中1081例(33.84%)诊断为MAFLD,其中男性698例(64.57%)、女性383例(35.43%),40～50年龄段人数最多有424例(39.22%),差异均有统计学意义(P<0.001)。病例组PNPLA3基因高甲基化状态2例(13.33%),对照组10例(66.67%),差异具有统计学意义(χ²=6.806, P=0.009);FABP1基因高甲基化状态5例(33.33%);对照组12例(80.00%),差异具有统计学意义(χ²=4.887, P=0.027)。PNPLA3基因甲基化状态与空腹血糖(FPG)(r=-0.385, P<0.05)、甘油三酯(TG)(r=-0.584, P<0.05)呈负相关,高密度脂蛋白(HDL-C)(r=0.651, P<0.001)呈正相关;FABP1基因甲基化状态与尿素(UA)(r=-0.407, P<0.05)、FPG(r=-0.416, P<0.05)、TG(r=-0.565, P<0.05)、总胆固醇(TC)(r=-0.515, P<0.05)、天冬氨酸氨基转移酶(AST)(r=-0.416, P<0.05)、丙氨酸氨基转移酶(ALT) (r=-0.473, P<0.05)呈负相关,与HDL-C(r=0.487, P<0.05)呈正相关。结论乌鲁木齐市MAFLD患病率处于全国高位。MAFLD患者血浆中PNPLA3、FABP1基因启动子区甲基化状态均明显降低,且与FPG、TG、TC、UA、AST、ALT和HDL-C相关,是MAFLD发生、发展的重要机制之一。

Abstract: Objective To investigate the prevalence of metabolic-associated fatty liver disease (MAFLD) in Urumqi, and to explore the association of the methylation of PNPLA3 and FABP1 genes with the incidence of MAFLD by comparing the methylation levels of PNPLA3 and FABP1 genes between MAFLD patients and normal people. Methods The clinical data of the population undergoing physical examination in the First Affiliated Hospital of Xinjiang Medical University from January to March 2022 were retrospectively analyzed. 15 patients with MAFLD were recruited as the case group, and 15 healthy people without previous history of liver diseases were matched at the same time as the control group. Methylation specific PCR (MSP) method was used to detect the methylation of PNPLA3 and FABP1 genes. Point-biserial correlation was used to analyze the correlation between clinical data and the genes expression. Results A total of 1081 cases (33.84%) in 3194 physical examination subjects were diagnosed as MAFLD, including 698 (64.57%) males, 383 (35.43%) females, and 424 cases (39.22%) with age of 40 to 50 years old, the differences were statistically significant (P<0.001). There were 2 cases (13.33%) in the case group and 10 cases (66.67%) in the control group had PNPLA3 gene hypermethylation, the difference was statistically significant (χ²=6.806, P=0.009). Similarly there were 5 cases (33.33%) in the case group and 12 cases (80.00%) in the control group had FABP1 gene hypermethylated status, the difference was statistically significant (χ²=4.887, P=0.027). The methylation status of PNPLA3 gene was negatively correlated with the levels of fasting blood glucose (FPG) (r=-0.385, P<0.05), triglyceride (TG)(r=-0.584, P<0.05), and high density lipoprotein (HDL-C)(r=0.651, P<0.001). The methylation status of FABP1 gene was negatively correlated with the serum levels of urea (UA) (r=0.407, P<0.05), FPG (r=0.416, P<0.05), TG (r=0.565, P<0.05), total cholesterol (TC) (r=0.515, P<0.05), aspertate aminotransferase (AST) (r=-0.416, P<0.05), alanine aminotransferase (ALT) (r=0.473, P<0.05), whereas positively correlated with the level of HDL-C (r=0.487, P<0.05). Conclusion The prevalence of MAFLD in Urumqi is the highest in China. The methylation status of PNPLA3 and FABP1 genes promoter region in blood cells of patients with MAFLD was significantly decreased, and was correlated with FPG, TG, TC, UA, AST, ALT, HDL-C and apolipoprotein B, which is one of the important mechanisms for the occurrence and development of MAFLD.

Key words: Metabolism-related fatty liver disease, Methylation, PNPLA3 gene, FABP1 genes, Correlation analysis

朱凯, 杨磊, 周青, 马雪儿, 李琴, 何晓萱, 杨雪霞, 蔡雯. PNPLA3和FABP1基因甲基化与代谢相关脂肪性肝病相关性分析[J]. 肝脏, 2023, 28(2): 207-213.

ZHU Kai, YANG Lei, ZHOU Qing, MA Xue-er, LI Qin, HE Xiao-xuan, YANG Xue-xia, CAI Wen. The association of PNPLA3 and FABP1 genes methylation with metabolism-related fatty liver disease[J]. Chinese Hepatolgy, 2023, 28(2): 207-213.

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