本文選題：酒精性肝病　切入點(diǎn)：單核苷酸多態(tài)性　出處：《吉林大學(xué)》2017年碩士論文

【摘要】：目的:酒精性肝病(alcoholic liver disease,ALD)是因長(zhǎng)期過(guò)量飲酒導(dǎo)致的一種慢性肝病,遺傳因素在其發(fā)病中具有重要作用。全基因組關(guān)聯(lián)分析研究(genome-wide association study,GWAS)發(fā)現(xiàn)PNPLA3、MBOAT7和TM6SF2基因與歐洲白種人群ALD患者相關(guān),但其是否與中國(guó)漢族人群ALD患者相關(guān)目前還尚未有研究報(bào)道。因此,本研究的目的是探討PNPLA3、MBOAT7和TM6SF2基因單核苷酸多態(tài)性(single nucleotide polymorphisms,SNP)與中國(guó)漢族人群ALD遺傳易感性的相關(guān)性,從而有助于ALD預(yù)防,并為ALD提供精準(zhǔn)的治療靶點(diǎn)。方法:本研究納入了507例ALD患者和645例健康對(duì)照,采用基質(zhì)輔助激光解吸電離飛行時(shí)間質(zhì)譜(Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry,MALDI-TOF MS)方法對(duì)PNPLA3、MBOAT7和TM6SF2基因的候選SNP位點(diǎn)rs738409、rs626283、rs641738、rs10401969和rs58542926進(jìn)行基因分型�；蚍中徒Y(jié)果使用PLINK 1.07軟件進(jìn)行分析。比較各SNP位點(diǎn)的等位基因和基因型頻率在ALD組和對(duì)照組之間的差異,并在三種遺傳模型(加性、顯性和隱性)下對(duì)各SNP位點(diǎn)進(jìn)行相關(guān)性分析。結(jié)果:PNPLA3基因的SNP位點(diǎn)rs738409等位基因和基因型頻率在疾病組和對(duì)照組間差異具有統(tǒng)計(jì)學(xué)意義(P=1.25×10-14和P=1.81×10-13)。與對(duì)照組相比G等位基因頻率和GG基因型頻率在ALD患者中明顯升高。在加性、顯性和隱性三種遺傳模型下基因型頻率差異也有統(tǒng)計(jì)學(xué)意義(P=1.07×10-13,P=9.3×10-8和P=1.57×10-12)。而rs62628、rs641738、rs10401969和rs58542926位點(diǎn)等位基因頻率和基因型頻率在兩組間差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:本研究發(fā)現(xiàn),PNPLA3基因多態(tài)性位點(diǎn)rs738409與中國(guó)漢族人群ALD易感性相關(guān),而MBOAT7(rs626283、rs641738)和TM6SF2(rs10401969、rs58542926)與中國(guó)漢族人群ALD患者遺傳易感性不相關(guān)。
[Abstract]:Objective: alcoholic liver disease (ALD) is a chronic liver disease caused by excessive drinking for a long time. Genetic factors play an important role in the pathogenesis of the disease. Genome-wide association studyGWASs have found that PNPLA3MBOAT7 and TM6SF2 genes are associated with ALD in European white population. However, the relationship between PNPLA3MBOAT7 and TM6SF2 gene single nucleotide polymorphismsSNPs (SNPs) and the genetic susceptibility of ALD in Chinese Han population has not been reported yet, so the purpose of this study is to explore the relationship between PNPLA3MBOAT7 and single nucleotide polymorphismsNPs (SNPs) in Chinese Han population. Methods: the study included 507 patients with ALD and 645 healthy controls. Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass spectrometric MALDI-TOF MS was used to type the candidate SNP loci rs738409rs626283rs64388rs10401969 and rs58542926 for PNPLA3MBOAT7 and TM6SF2 genes. The genotyping results were analyzed by PLINK 1.07 software. The allele and genotype frequency of SNP locus were different between ALD group and control group. And in three genetic models (additive, Results the rs738409 alleles and genotype frequencies of SNP locus in the SNP locus of the 1: PNPLA3 gene were significantly different between the disease group and the control group (P = 1.25 脳 10 ~ (-14) and P ~ (1.81) 脳 10 ~ (-13)), respectively. Compared with the control group, the G allele was higher than that of the control group. Gene frequency and GG genotype frequency were significantly increased in patients with ALD. There were also significant differences in genotype frequencies between dominant and recessive genetic models (P = 1.07 脳 10 ~ (-13) P 9.3 脳 10 ~ (-8) and P ~ (1.57) 脳 10 ~ (-12)), while the allele frequencies and genotype frequencies of rs62628 / rs641738 / s 10401969 and rs58542926 loci were not significantly different between the two groups (P _ (0.05)). Conclusion: this study found no significant difference in allele frequencies and genotype frequencies of PNPLA3 between the two groups. Gene polymorphism locus (rs738409) was associated with susceptibility to ALD in Chinese Han population. MBOAT7 rs626283 (rs641738) and TM6SF2 rs10401969rs58542926) were not associated with genetic susceptibility to ALD in Chinese Han population.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R575

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 張龍玉;閆亮;郝書(shū)理;葉文華;張紀(jì)元;李保森;黃昂;田輝;劉西秦;鄒正升;;乙醛脫氫酶2基因多態(tài)性與酒精性肝病患者飲酒特點(diǎn)和疾病發(fā)生的關(guān)系[J];實(shí)用肝臟病雜志;2016年03期

相關(guān)碩士學(xué)位論文 前1條

1 高超;PNPLA3基因多態(tài)性與酒精性肝病遺傳易感性的相關(guān)性研究[D];山西醫(yī)科大學(xué);2014年

，

本文編號(hào)：1672702