本文選題：非酒精性脂肪肝 + 基因多態(tài)性�。� 參考：《大連醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景:非酒精性脂肪性肝病(Nonalcoholic fatty liver disease,NAFLD)是世界各地的一個(gè)日益嚴(yán)重的醫(yī)療問題,可能發(fā)展為肝硬化和肝細(xì)胞癌。通過研究NAFLD的發(fā)病機(jī)制,用以明確NAFLD的預(yù)防及治療具有十分重要的臨床意義。目前認(rèn)為NAFLD的發(fā)病是基因、環(huán)境等多因素共同作用的結(jié)果,其中遺傳因素的作用舉足輕重。分揀蛋白1(Sort1)是一個(gè)脂質(zhì)代謝調(diào)節(jié)基因,其編碼的分揀蛋白(sortilin)是載脂蛋白胞內(nèi)受體。Sort1基因多態(tài)性已被證實(shí)與脂質(zhì)代謝相關(guān),而肝臟和周圍組織的脂質(zhì)代謝紊亂是NAFLD發(fā)生發(fā)展的直接機(jī)制,目前尚缺乏Sort1與NAFLD的相關(guān)研究。目的:本文旨在探討我國北方漢族人群Sort1基因單核苷酸多態(tài)性(SNP)位點(diǎn)rs646776對(duì)血脂水平的影響,以及與NAFLD發(fā)病風(fēng)險(xiǎn)的相關(guān)性。方法:本研究是基于北方地區(qū)漢族群體的病例-對(duì)照研究。收集來自青島市市立醫(yī)院的294名NAFLD患者和296名健康人群的血液標(biāo)本,交由生物公司對(duì)Sort1 rs646776進(jìn)行基因檢測。通過哈迪-溫伯格(H-W)平衡法則分析病例組及對(duì)照組基因型是否具有群體代表性,并測量兩組各項(xiàng)臨床指標(biāo)(如性別、年齡、體重指數(shù)等)及血清生物化學(xué)指標(biāo)(如ALT、AST、TG、LDL等),比較NAFLD組及正常對(duì)照組相關(guān)臨床資料的差異以及Sort1 rs646776基因型和等位基因頻率的差異,分析Sort1 rs646776對(duì)NAFLD的發(fā)病風(fēng)險(xiǎn)。比較不同基因組血脂相關(guān)指標(biāo)水平。本實(shí)驗(yàn)采用SPSS20.0軟件包進(jìn)行相關(guān)統(tǒng)計(jì)學(xué)數(shù)據(jù)分析。Pearson φ2和t檢驗(yàn)分別用于計(jì)數(shù)單位以及計(jì)量單位比較,采用非條件Logistic回歸模型分析計(jì)算優(yōu)勢(shì)比(OR)及其95%可信區(qū)間(95%CI)。結(jié)果:NAFLD組與對(duì)照組比較,性別具有統(tǒng)計(jì)學(xué)差異(P0.05),NAFLD組年齡、BMI、血壓均高于對(duì)照組,差異具有統(tǒng)計(jì)學(xué)意義(P0.05),在實(shí)驗(yàn)室檢查方面,NAFLD組ALT、AST、GGT、ALP、FPG、TG、TC及LDL均高于正常對(duì)照組,差異具有統(tǒng)計(jì)學(xué)意義(P0.05);HDL低于對(duì)照組,差異亦具有統(tǒng)計(jì)學(xué)意義(P0.05)。Sort1基因rs646776位點(diǎn)在NAFLD組與對(duì)照組之間的等位基因頻率及基因型分布頻率差異有統(tǒng)計(jì)學(xué)意義(χ2=5.389,P=0.020;φ2=6.572,P=0.037)。非條件Logistic回歸分析結(jié)果顯示,攜帶T等位基因者相對(duì)于攜帶C等位基因者NAFLD患病風(fēng)險(xiǎn)高1.719倍(OR=1.719,95%CI = 1.083～2.727,P=0.022),經(jīng)過性別、年齡、體重指數(shù)等混雜因素校正后,T等位基因攜帶者NAFLD患病風(fēng)險(xiǎn)是C等位基因攜帶者的 1.443 倍(0R=1.443,95%CI=0.812～2.564,P0.05),差異無統(tǒng)計(jì)學(xué)意義。在合并人群中,CC基因型較TC/TT基因型有較高的HDL-C水平(P=0.000),有較低的TG水平(P=0.042),較TC+TT基因型在HDL-C水平與TG水平同樣有統(tǒng)計(jì)學(xué)意義(P=0.000;P=0.030)。結(jié)論:在我國北方地區(qū)漢族人群中,Sort1基因rs646776位點(diǎn)多態(tài)性與血脂水平相關(guān),與NAFLD的患病風(fēng)險(xiǎn)不具有相關(guān)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.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R575
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本文編號(hào)：1863252