中国汉族人群酒精性肝病的候选基因关联分析研究

发布时间：2018-03-27 18:25

本文选题：酒精性肝病　切入点：单核苷酸多态性　出处：《吉林大学》2017年硕士论文

【摘要】：目的:酒精性肝病(alcoholic liver disease,ALD)是因长期过量饮酒导致的一种慢性肝病,遗传因素在其发病中具有重要作用。全基因组关联分析研究(genome-wide association study,GWAS)发现PNPLA3、MBOAT7和TM6SF2基因与欧洲白种人群ALD患者相关,但其是否与中国汉族人群ALD患者相关目前还尚未有研究报道。因此,本研究的目的是探讨PNPLA3、MBOAT7和TM6SF2基因单核苷酸多态性(single nucleotide polymorphisms,SNP)与中国汉族人群ALD遗传易感性的相关性,从而有助于ALD预防,并为ALD提供精准的治疗靶点。方法:本研究纳入了507例ALD患者和645例健康对照,采用基质辅助激光解吸电离飞行时间质谱(Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry,MALDI-TOF MS)方法对PNPLA3、MBOAT7和TM6SF2基因的候选SNP位点rs738409、rs626283、rs641738、rs10401969和rs58542926进行基因分型。基因分型结果使用PLINK 1.07软件进行分析。比较各SNP位点的等位基因和基因型频率在ALD组和对照组之间的差异,并在三种遗传模型(加性、显性和隐性)下对各SNP位点进行相关性分析。结果:PNPLA3基因的SNP位点rs738409等位基因和基因型频率在疾病组和对照组间差异具有统计学意义(P=1.25×10-14和P=1.81×10-13)。与对照组相比G等位基因频率和GG基因型频率在ALD患者中明显升高。在加性、显性和隐性三种遗传模型下基因型频率差异也有统计学意义(P=1.07×10-13,P=9.3×10-8和P=1.57×10-12)。而rs62628、rs641738、rs10401969和rs58542926位点等位基因频率和基因型频率在两组间差异均无统计学意义(P0.05)。结论:本研究发现,PNPLA3基因多态性位点rs738409与中国汉族人群ALD易感性相关,而MBOAT7(rs626283、rs641738)和TM6SF2(rs10401969、rs58542926)与中国汉族人群ALD患者遗传易感性不相关。
[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.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R575

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