本文選題：煤工塵肺 + 候選基因��； 參考：《華北理工大學》2017年碩士論文

【摘要】：目的近期的全基因組關聯分析(Genome-wide association study,GWAS)和候選基因關聯分析發(fā)現多個基因與肺纖維化相關,包括橋粒斑蛋白基因(DSP)、家族序列相似性13A基因(FAM13A)、二肽基肽酶9基因(DPP9)、端粒酶逆轉錄酶基因(TERT)、端粒酶RNA基因(TERC)、核組裝因子1基因(NAF1)和細胞色素b245α基因(CYBA)。本研究旨在探討上述7個候選基因單核苷酸多態(tài)性(Single nucleotide polymorphisms,SNP)與煤工塵肺(Coal workers,pneumoco niosis,CWP)的相關性,從而為CWP高危人群的早期篩查及遺傳學機制研究提供理論依據。方法本研究采用病例-對照的研究方法,研究對象包括652例CWP患者和648例接塵對照者。通過基質輔助激光解吸電離飛行時間質譜技術(Matrix-assisted las er desorption/ionization time of flight mass spectrometry,MALDI-TOF MS),對16個SNP位點進行分型。應用PLink1.07軟件分析各SNP位點基因型和等位基因頻率分布差異,同時在相加模型、顯性模型和隱性模型下分析各SNP位點與CWP的相關性。利用SHEsis軟件進行連鎖不平衡及單體型頻率分析。采用SPSS17.0統(tǒng)計軟件對相關數據處理分析。以P0.05為差異具有統(tǒng)計學意義。結果1卡方分析結果顯示,TERT基因rs2736100位點、NAF1基因rs4691896和rs3822304位點及CYBA基因rs7195830位點的基因型及等位基因頻率在CWP組與接塵對照組比較,差異有統(tǒng)計學意義(P0.05)。CWP組TERT基因rs2736100位點C等位基因頻率低于接塵對照組(OR=0.840,95%CI=0.717-0.984,P=0.031)。CWP組NAF1基因rs4691896位點T等位基因和rs3822304位點G等位基因頻率均顯著高于接塵對照組(OR=1.891,95%CI=1.536-2.330,P0.001;OR=1.9622,95%CI=1.167-3.300,P=0.010)。CWP組CYBA基因rs7195830位點A等位基因頻率顯著高于接塵對照組(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位點的基因型和等位基因頻率,CWP組與接塵對照組比較差異均無統(tǒng)計學意義(P0.05)。2遺傳模型結果顯示,TERT基因rs2736100和NAF1基因rs3822304位點在相加模型下與CWP有關(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位點在相加模型和顯性模型下均與CWP有關(OR=1.961,95%CI=1.579-2.436,P0.001;OR=1.671,95%CI=1.142-2.442,P=0.008)。同樣,CYBA基因rs7195830位點在相加模型及顯性模型下均與CWP有關(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位點在三種遺傳模型下均與CWP無關(P0.05)。3單體型結果顯示,NAF1基因rs7675998、rs4691896和rs936562構成的ACA、ATA、GCT和GTA單體型在CWP組中的頻率分別為0.2%、17.5%、77.5%和4.3%,在接塵對照中相應的頻率為5.7%、10.3%、78.6%和2.5%,兩組之間單體型ACA、ATA和GTA頻率差異有統(tǒng)計學意義(P0.05),兩組之間單體型GCT頻率差異無統(tǒng)計學意義(P0.05)。結論1 TERT基因rs2736100、NAF1基因(rs4691896和rs3822304)及CYBA基因rs7195830位點與CWP相關,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構成的ACA、ATA和GTA單體型與CWP有關。
[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.
【學位授予單位】：華北理工大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R135.2;R440

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