Sort1基因rs646776位点多态性与非酒精性脂肪性肝病的相关性研究

发布时间：2018-05-08 22:03

  本文选题：非酒精性脂肪肝 + 基因多态性　； 参考：《大连医科大学》2017年硕士论文

【摘要】：背景:非酒精性脂肪性肝病(Nonalcoholic fatty liver disease,NAFLD)是世界各地的一个日益严重的医疗问题,可能发展为肝硬化和肝细胞癌。通过研究NAFLD的发病机制,用以明确NAFLD的预防及治疗具有十分重要的临床意义。目前认为NAFLD的发病是基因、环境等多因素共同作用的结果,其中遗传因素的作用举足轻重。分拣蛋白1(Sort1)是一个脂质代谢调节基因,其编码的分拣蛋白(sortilin)是载脂蛋白胞内受体。Sort1基因多态性已被证实与脂质代谢相关,而肝脏和周围组织的脂质代谢紊乱是NAFLD发生发展的直接机制,目前尚缺乏Sort1与NAFLD的相关研究。目的:本文旨在探讨我国北方汉族人群Sort1基因单核苷酸多态性(SNP)位点rs646776对血脂水平的影响,以及与NAFLD发病风险的相关性。方法:本研究是基于北方地区汉族群体的病例-对照研究。收集来自青岛市市立医院的294名NAFLD患者和296名健康人群的血液标本,交由生物公司对Sort1 rs646776进行基因检测。通过哈迪-温伯格(H-W)平衡法则分析病例组及对照组基因型是否具有群体代表性,并测量两组各项临床指标(如性别、年龄、体重指数等)及血清生物化学指标(如ALT、AST、TG、LDL等),比较NAFLD组及正常对照组相关临床资料的差异以及Sort1 rs646776基因型和等位基因频率的差异,分析Sort1 rs646776对NAFLD的发病风险。比较不同基因组血脂相关指标水平。本实验采用SPSS20.0软件包进行相关统计学数据分析。Pearson φ2和t检验分别用于计数单位以及计量单位比较,采用非条件Logistic回归模型分析计算优势比(OR)及其95%可信区间(95%CI)。结果:NAFLD组与对照组比较,性别具有统计学差异(P0.05),NAFLD组年龄、BMI、血压均高于对照组,差异具有统计学意义(P0.05),在实验室检查方面,NAFLD组ALT、AST、GGT、ALP、FPG、TG、TC及LDL均高于正常对照组,差异具有统计学意义(P0.05);HDL低于对照组,差异亦具有统计学意义(P0.05)。Sort1基因rs646776位点在NAFLD组与对照组之间的等位基因频率及基因型分布频率差异有统计学意义(χ2=5.389,P=0.020;φ2=6.572,P=0.037)。非条件Logistic回归分析结果显示,携带T等位基因者相对于携带C等位基因者NAFLD患病风险高1.719倍(OR=1.719,95%CI = 1.083～2.727,P=0.022),经过性别、年龄、体重指数等混杂因素校正后,T等位基因携带者NAFLD患病风险是C等位基因携带者的 1.443 倍(0R=1.443,95%CI=0.812～2.564,P0.05),差异无统计学意义。在合并人群中,CC基因型较TC/TT基因型有较高的HDL-C水平(P=0.000),有较低的TG水平(P=0.042),较TC+TT基因型在HDL-C水平与TG水平同样有统计学意义(P=0.000;P=0.030)。结论:在我国北方地区汉族人群中,Sort1基因rs646776位点多态性与血脂水平相关,与NAFLD的患病风险不具有相关性。
[Abstract]:Background: nonalcoholic fatty liver disease (NAFLD) is an increasingly serious medical problem in various parts of the world, which may develop into cirrhosis and hepatocellular carcinoma. By studying the pathogenesis of NAFLD, it is of great clinical significance to clarify the prevention and treatment of NAFLD. At present, it is believed that the pathogenesis of NAFLD is the result of multiple factors such as gene and environment, among which genetic factors play an important role. Sortilinis an apolipoprotein receptor. Sort1 gene polymorphism has been proved to be associated with lipid metabolism. However, the disorder of lipid metabolism in liver and surrounding tissues is the direct mechanism of the occurrence and development of NAFLD. At present, there is a lack of research on Sort1 and NAFLD. Objective: to investigate the effect of Sort1 gene single nucleotide polymorphism (SNPN) rs646776 on serum lipids and its association with the risk of NAFLD in northern Chinese Han population. Methods: this study was based on a case-control study of Han population in northern China. Blood samples from 294 NAFLD patients and 296 healthy people from Qingdao City Hospital were collected for genetic analysis of Sort1 rs646776 by a biological company. To analyze whether the genotype of the case group and the control group is representative of the population, and to measure the clinical indexes (such as sex, age, etc.) by using the H-Wal rule of Hardy Weinberg. Body mass index (BMI) and serum biochemical indexes (such as alt AST TGG, LDL, etc.) were compared between NAFLD group and normal control group, and the differences of Sort1 rs646776 genotype and allele frequency were compared, and the risk of NAFLD was analyzed by Sort1 rs646776. The relative indexes of blood lipid in different genomes were compared. Pearson 蠁 2 and t test were used to compare counting units and measuring units by SPSS20.0 software package. The odds ratio (OR) and 95% confidence interval (95% CI) were calculated by non conditional Logistic regression model. Results compared with the control group, there was statistical difference between the two groups. The age and blood pressure of the NAFLD group was higher than that of the control group, and the difference was statistically significant (P 0.05). The TC and LDL of the NAFLD group were higher than those of the normal control group. There were significant differences in the allele frequency and genotype distribution between the NAFLD group and the control group (蠂 25.389 P0.020; 蠁 26.572P0.0377.The difference was statistically significant between the NAFLD group and the control group in the rs646776 locus of the P0.05. Sort1 gene), and the difference was also significant between the NAFLD group and the control group (P 0.020; P 0.020; P 0.020; P 0.020; P 0.020; P 0.020; P 0.020; P 0.020; P 0.020; P 0.020; The results of non-conditional Logistic regression analysis showed that the risk of NAFLD in T allele carriers was 1.719 times higher than that in C alleles. The NAFLD risk of T allele carriers adjusted for body mass index was 1.443 times higher than that of C allele carriers, and there was no significant difference between them. In the combined population, the HDL-C level of CC genotype was higher than that of TC/TT genotype, and the level of TG was lower than that of TCTT genotype. There was significant difference between TCTT genotype and TG level in HDL-C level. Conclusion: the polymorphism of rs646776 locus of Sort1 gene is associated with the level of blood lipids, but not with the risk of NAFLD in the Han population in northern China.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R575
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本文编号：1863252