中国汉族人群多发性骨髓瘤的候选基因关联性研究

发布时间：2018-05-24 23:39

本文选题：多发性骨髓瘤 + NCOA1　；参考：《郑州大学》2017年硕士论文

【摘要】：研究背景多发性骨髓瘤(Multiple myeloma,MM)是一种不可治愈的成熟B淋巴细胞恶性肿瘤,其发病机制仍不完全清楚。之前的研究表明,许多非霍奇金淋巴瘤(Non-Hodgkin Lymphoma,NHL)的相关基因同样与MM的易感性相关,表明源自B细胞的恶性肿瘤可能共享基因的遗传易感性。滤泡性淋巴瘤(follicular lymphoma,FL)和弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)是两种常见的NHL。最近的几项大规模全基因组关联分析(genome-wide association studies,GWAS)发现HLA-I,HLA-II,CXCR5,ETS1,LPP和NCOA1基因是FL和DLBCL的候选基因,但这些基因上的SNP位点是否与中国汉族人群MM相关还有待研究。目的探讨HLA I(rs6457327)、HLA II(rs2647012和rs7755224)、CXCR5(rs4938573)、ETS1(rs4937362)、LPP(rs6444305)和NCOA1(rs79480871)与中国汉族人群MM及MM临床指标之间的关联。方法本研究属于病例-对照设计,收集了中国汉族人群中的827例MM患者和709例健康对照者的样本。选择HLA I类基因上的rs6457327、HLA II类基因上的rs2647012和rs7755224、CXCR5基因上的rs4938573、ETS1基因上的rs4937362、LPP基因上的rs6444305和NCOA1基因上的rs79480871,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)方法对以上6个基因上的7个SNP位点进行基因分型。结果NCOA1基因上的位点rs79480871的等位基因和基因型频率的结果均显示与MM疾病显著相关(pa=3.5×10-4,pa=1.5×10-4)。HLA-I类基因上的位点rs6457327的基因型频率在病例组和对照组之间存在显著的差异(pa=4.9×10-3)。NCOA1基因上的rs79480871的病例组和对照组在加性和显性模型中有显著的差异(pa=1.1×10-4,pa=2.1×10-4)。HLA-I类基因上的rs6457327在显性模型和EST1基因上的rs4937362在隐性模型下的差异有统计学意义(pa=0.03,pa=0.048)。这些SNP位点与低Hb水平、低Alb水平、高Crea水平、高β2-MG水平均不相关(p0.05)。结论NCOA1基因可能是中国汉族人群MM患者的易感基因,且NCOA1基因可能作为共同的遗传因素在MM和NHL的发病机制中起作用。
[Abstract]:Background multiple myeloma MMM (multiple myeloma) is an incurable mature B lymphocyte malignant tumor, the pathogenesis of which is still unclear. Previous studies have shown that many non-Hodgkin Lymphomia NHL genes are also associated with MM susceptibility, suggesting that malignant tumors originating from B cells may share genetic susceptibility. Follicular lymphomatosis (FLL) and diffuse large B-cell lymphoma (DLBCLs) are two common NHLLs. Recently, several large-scale genome-wide association studies-GWASs have found that HLA-IHA-CXCR5ETS1LPP and NCOA1 genes are candidate genes for FL and DLBCL. However, whether the SNP locus of these genes is related to MM in Chinese Han population remains to be studied. Objective to investigate the relationship between HLA rs6457327 II(rs2647012 and rs7755224CXCR5 rs4938573 (ETS1) rs4937362 (LPPs6444305) and NCOA1 rs79480871) and the clinical parameters of MM and MM in Chinese Han population. Methods 827 MM patients and 709 healthy controls were collected from Chinese Han population. The rs2647012 on rs6457327 and rs7755224CXCR5 gene and rs4938573 on rs4937362LPP gene and rs79480871 on NCOA1 gene were selected. The matrix assisted laser desorption ionization time of flight mass spectrometry (Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometric MAMALDI-TOF MS) was used. Seven SNP loci of the 6 genes were genotyped. Results the results of allele and genotype frequency of rs79480871 on the NCOA1 gene showed that there was a significant difference in the genotype frequency of rs6457327 on the 1.5 脳 10-4).HLA-I class gene between the case group and the control group. There was a significant difference between the case group and the control group in the genotype frequency of rs6457327. 4. 9 脳 10-3).NCOA1 gene. There was significant difference between the case group of rs79480871 and the control group in the additive and dominant models. There was a significant difference between the dominant model and the rs4937362 of the EST1 gene in the dominant model and the rs4937362 on the EST1 gene in the dominant model and in the recessive model respectively. These SNP loci were not correlated with low HB level, low Alb level, high Crea level and high 尾 2-MG level. Conclusion NCOA1 gene may be the susceptibility gene of MM patients in Chinese Han population, and NCOA1 gene may play a role in the pathogenesis of MM and NHL as a common genetic factor.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R733.3

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