煤工尘肺候选基因单核苷酸多态性的关联分析研究

发布时间：2018-05-21 19:40

本文选题：煤工尘肺 + 候选基因　；参考：《华北理工大学》2017年硕士论文

【摘要】：目的近期的全基因组关联分析(Genome-wide association study,GWAS)和候选基因关联分析发现多个基因与肺纤维化相关,包括桥粒斑蛋白基因(DSP)、家族序列相似性13A基因(FAM13A)、二肽基肽酶9基因(DPP9)、端粒酶逆转录酶基因(TERT)、端粒酶RNA基因(TERC)、核组装因子1基因(NAF1)和细胞色素b245α基因(CYBA)。本研究旨在探讨上述7个候选基因单核苷酸多态性(Single nucleotide polymorphisms,SNP)与煤工尘肺(Coal workers,pneumoco niosis,CWP)的相关性,从而为CWP高危人群的早期筛查及遗传学机制研究提供理论依据。方法本研究采用病例-对照的研究方法,研究对象包括652例CWP患者和648例接尘对照者。通过基质辅助激光解吸电离飞行时间质谱技术(Matrix-assisted las er desorption/ionization time of flight mass spectrometry,MALDI-TOF MS),对16个SNP位点进行分型。应用PLink1.07软件分析各SNP位点基因型和等位基因频率分布差异,同时在相加模型、显性模型和隐性模型下分析各SNP位点与CWP的相关性。利用SHEsis软件进行连锁不平衡及单体型频率分析。采用SPSS17.0统计软件对相关数据处理分析。以P0.05为差异具有统计学意义。结果1卡方分析结果显示,TERT基因rs2736100位点、NAF1基因rs4691896和rs3822304位点及CYBA基因rs7195830位点的基因型及等位基因频率在CWP组与接尘对照组比较,差异有统计学意义(P0.05)。CWP组TERT基因rs2736100位点C等位基因频率低于接尘对照组(OR=0.840,95%CI=0.717-0.984,P=0.031)。CWP组NAF1基因rs4691896位点T等位基因和rs3822304位点G等位基因频率均显著高于接尘对照组(OR=1.891,95%CI=1.536-2.330,P0.001;OR=1.9622,95%CI=1.167-3.300,P=0.010)。CWP组CYBA基因rs7195830位点A等位基因频率显著高于接尘对照组(OR=1.550,95%CI=1.289-1.863,P0.001)。DSP基因rs2076295、CYBA基因(rs13306296、rs4673、rs9932581和rs16966671)、TERC基因(rs10936599和rs12696304)、NAF1基因(rs7675998、rs12331717和rs936562)、DPP9基因rs12610495和FAM13A基因rs2609255位点的基因型和等位基因频率,CWP组与接尘对照组比较差异均无统计学意义(P0.05)。2遗传模型结果显示,TERT基因rs2736100和NAF1基因rs3822304位点在相加模型下与CWP有关(OR=0.844,95%CI=0.722-0.987,P=0.034;OR=1.959,95%CI=1.164-3.295,P=0.011)。NAF1基因rs4691896位点在相加模型和显性模型下均与CWP有关(OR=1.961,95%CI=1.579-2.436,P0.001;OR=1.671,95%CI=1.142-2.442,P=0.008)。同样,CYBA基因rs7195830位点在相加模型及显性模型下均与CWP有关(OR=1.621,95%CI=1.334-1.970,P0.001;OR=1.711,95%CI=1.197,P=0.003)。DSP基因rs2076295、CYBA基因(rs13306296、rs4673、rs9932581和rs16966671)、TERC基因(rs10936599和rs12696304)、NAF1基因(rs7675998、rs12331717和rs936562)、DPP9基因rs12610495和FAM13A基因rs2609255位点在三种遗传模型下均与CWP无关(P0.05)。3单体型结果显示,NAF1基因rs7675998、rs4691896和rs936562构成的ACA、ATA、GCT和GTA单体型在CWP组中的频率分别为0.2%、17.5%、77.5%和4.3%,在接尘对照中相应的频率为5.7%、10.3%、78.6%和2.5%,两组之间单体型ACA、ATA和GTA频率差异有统计学意义(P0.05),两组之间单体型GCT频率差异无统计学意义(P0.05)。结论1 TERT基因rs2736100、NAF1基因(rs4691896和rs3822304)及CYBA基因rs7195830位点与CWP相关,TERT基因、NAF1基因和CYBA基因可能是CWP的易感基因。2 NAF1基因rs7675998、rs4691896和rs936562构成的ACA、ATA和GTA单体型与CWP有关。
[Abstract]:Objective the recent Genome-wide association study (GWAS) and candidate gene association analysis found that multiple genes were associated with pulmonary fibrosis, including the PMR gene (DSP), family sequence similarity 13A (FAM13A), two peptidyl peptidase 9 gene (DPP9), telomerase reverse transcriptase gene (TERT), telomerase RNA gene (TER) C), nuclear assembly factor 1 gene (NAF1) and cytochrome b245 alpha gene (CYBA). This study aims to explore the correlation between the above 7 candidate gene polymorphisms (Single nucleotide polymorphisms, SNP) and coal workers' pneumoconiosis (Coal workers, pneumoco niosis), so as to provide an early screening and genetic mechanism for the high-risk population. A case control study was used in this study. The subjects included 652 patients with CWP and 648 Cases of dust control. The 16 sites were performed by matrix assisted laser desorption ionization time of flight mass spectrometry (Matrix-assisted las er desorption/ionization time of flight mass spectrometry, MALDI-TOF MS). PLink1.07 software was used to analyze the difference in frequency distribution of genotype and allele of SNP loci. At the same time, the correlation between SNP loci and CWP was analyzed under the additive model, dominant model and recessive model. The linkage disequilibrium and haplotype frequency analysis were analyzed by SHEsis software. The related data were processed and analyzed by SPSS17.0 software. Results the difference was statistically significant. Results 1 chi square analysis showed that the genotype and allele frequencies of the TERT gene rs2736100 locus, the NAF1 gene rs4691896 and rs3822304 loci and the CYBA gene rs7195830 loci were compared in the CWP group with the dust control group, and the difference was statistically significant (P0.05).CWP group TERT gene allelic sites. The allele frequencies of rs4691896 loci and rs3822304 loci G of the NAF1 gene of the NAF1 gene in the group.CWP group (OR=0.840,95%CI=0.717-0.984, P=0.031) were significantly higher than those in the dust control group (OR=1.891,95%CI=1.536-2.330, P0.001; OR=1.9622,95%CI=1.167-3.300, P=0.010) allele frequency The rate was significantly higher than that of the OR=1.550,95%CI=1.289-1.863 (P0.001).DSP gene rs2076295, the CYBA gene (rs13306296, rs4673, rs9932581 and rs16966671), the TERC gene (rs10936599 and rs12696304), the genotype and allele frequency of the gene and the allele. The difference was not statistically significant between the CWP group and the control group (P0.05). The.2 genetic model showed that the rs3822304 locus of the TERT gene rs2736100 and NAF1 gene was associated with CWP (OR=0.844,95%CI=0.722-0.987, P=0.034; OR=1.959,95%CI=1.164-3.295, P= 0.011) in the additive model and the dominant model. All of them are related to CWP (OR=1.961,95%CI=1.579-2.436, P0.001; OR=1.671,95%CI=1.142-2.442, P=0.008). Similarly, the rs7195830 loci of the CYBA gene are related to CWP (OR=1.621,95%CI=1.334-1.970, P0.001; OR=1.711,95%CI=1.197, P=0.003). 66671), the TERC gene (rs10936599 and rs12696304), the NAF1 gene (rs7675998, rs12331717 and rs936562), the rs12610495 and FAM13A gene rs2609255 loci of the DPP9 gene are shown under the three genetic models. Frequencies of 0.2%, 17.5%, 77.5% and 4.3% respectively were 5.7%, 10.3%, 78.6% and 2.5% in the dust control. There was a significant difference in the frequencies of ACA, ATA and GTA between the two groups (P0.05), and there was no significant difference in the frequency of GCT between the two groups (P0.05). Conclusion the 1 TERT gene rs2736100, NAF1 gene (rs4691896 and rs3822304) and CY The rs7195830 locus of the BA gene is associated with CWP, and the TERT, NAF1 and CYBA genes may be the CWP's susceptible gene.2 NAF1 rs7675998, rs4691896 and rs936562 constitute the somatotype.
【学位授予单位】：华北理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R135.2;R440

【参考文献】