MIP-1α基因多态性与宁夏海原地区结核病的关联研究

发布时间：2018-07-27 17:05

【摘要】：目的CC亚家族趋化因子巨噬细胞炎性蛋白-1α(macrophage inflammatory protein1-α，MIP-1α,CCL-3)在临床水平与疾病关联的研究也越来越受重视，在基因水平研究MIP-1α与疾病的预防、发生、发展和预后的判断也是越来越受到众多医学科学工作者的关注。MIP-1α对巨噬细胞、单核细胞均有趋化活性，并且能诱导产生炎症细胞因子，从而可以影响肉芽肿的发生和发展。MIP-1α基因的单核苷酸多态性（SNP）与疾病的相关性也逐步被人们所认识。本课题通过对MIP-1α基因rs1130371（C/T）、rs1719134（A/G）两个多态性位点与结核病的关联性研究来探讨其与宁夏海原地区结核病遗传易感性的关联。方法本研究采用以医院为基础的病例-对照研究设计，选择宁夏海原地区154例临床确诊为结核病的病例组，，平均年龄（43.41±19.65），男女比例为79:75，选取与其性别年龄相匹配的宁夏海原地区的190例健康人群作为对照组，平均年龄在（43.11±15.90），男女比例为91:99。用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）对rs1719134(A/G)位点进行基因分型；随机选取各100例病例和对照样本，平均年龄分别为43.36±22.36（病例组）和42.35±21.97（对照组），男女比例分别为57:43和59:41，用测序的方法对rs1130371(C/T)进行基因分型。用SPSS11.5统计学软件分别计算其基因型、等位基因频率，并进行卡方检验；同时用SHE sis软件对2个SNP位点进行连锁不平衡分析。对MIP-1α基因rs1719134和RANTES IN1.1位点、403位点、28位点用SHEsis软件进行连锁不平衡分析。结果1MIP-1α基因rs1719134位点与结核病的遗传易感性的相关性分析结果： 1.1宁夏海原地区样本rs1719134位点基因型和等位基因分布：病例组AA基因型为27.9%，AG基因型为63.0%，GG基因型为9.1%，对照组中AA基因型为17.9%，AG基因型为71.1%，GG基因型为11.1%。用SPSS软件进行卡方检验，结果显示其分布在病例组和对照组中有统计学差异（P=0.027,OR=1.777（1.066-2.964））；病例组中A等位基因为59.4%，G等位基因为40.6%，对照组中A等位基因为40.6%，G等位基因为59.4%。用SPSS软件进行卡方检验，结果显示其分布在病例组和对照组中无统计学差异（P0.05）。 2MIP-1α基因rs1130371位点与结核病的遗传易感性的相关性分析结果：随机选择病例组和对照组各100例进行测序分析，结果显示CC,CT基因型和等位基因C,T在病例对照样本中分布无显著性差异（P0.05），本实验发现总样本200例均无TT基因型。 3用SHE sis软件对MIP-1α基因rs1130371和rs1719134进行连锁不平衡分析，D’值为0.209，r2值为0.003，说明这两个SNP位点连锁不平衡关系不紧密。 4对MIP-1α基因rs1130371,rs1719134和RANTES IN1.1位点，403位点，28位点各基因型用SHE sis软件进行连锁不平衡分析，D’值均0.8，表明MIP-1α基因和RANTES基因SNP位点连锁不平衡关系不紧密。结论1MIP-1α基因rs1719134（A/G）与宁夏海原地区样本中结核病的发病有一定的关联性，其野生型AA基因型可能和宁夏海原地区结核病发病有关联。 2MIP-1α基因rs1130371（C/T）在200例样本中只有CC,CT两种基因型，没有发现TT基因型。CC，CT基因型的分布在病例对照组中分布无统计学差异。
[Abstract]:Objective CC subfamily chemokine macrophage inflammatory protein -1 alpha (macrophage inflammatory protein1- a, MIP-1 alpha, CCL-3) is becoming more and more important in the study of the association between the clinical level and the disease. At the gene level, the study of the prevention, occurrence, development and prognosis of MIP-1 A and the disease is also becoming more and more widely used by medical scientists. It is concerned that.MIP-1 alpha has chemotaxis to macrophages and monocytes, and can induce the production of inflammatory cytokines, which can affect the occurrence of granuloma and the development of the single nucleotide polymorphisms of the.MIP-1 a gene (SNP) and the correlation of the disease. This lesson is based on the MIP-1 alpha gene rs1130371 (C/T), rs1719134 (A/G). The association between two polymorphisms and tuberculosis was investigated to explore the association between genetic polymorphisms and genetic susceptibility to tuberculosis in Haiyuan, Ningxia.
Methods a case-control study based on the hospital was used in this study to select 154 cases of tuberculosis in the Haiyuan region of Ningxia. The average age (43.41 + 19.65) and the ratio of male and female were 79:75, and 190 healthy people in Ningxia Haiyuan region, which matched their sex and age, were selected as the control group, the average age was (43.11 + 15). .90), the proportion of men and women was 91:99. using polymerase chain reaction restriction fragment length polymorphism analysis (PCR-RFLP) to genotyping rs1719134 (A/G) loci; randomly selected 100 cases and control samples, the average age was 43.36 + 22.36 (case group) and 42.35 + 21.97 (control group). The ratio of men and women was 57:43 and 59:41, respectively, by sequencing. Methods the genotyping of rs1130371 (C/T) was carried out. The genotype, allele frequency and chi square test were calculated with SPSS11.5 statistics software, and the linkage disequilibrium analysis of 2 SNP loci was carried out with SHE SIS software. The MIP-1 alpha gene rs1719134 and RANTES IN1.1 sites, 403 loci, and 28 loci were linked by SHEsis software. Balance analysis.
Results the correlation between the rs1719134 locus of 1MIP-1 alpha gene and the genetic susceptibility of tuberculosis was analyzed.
1.1 the genotype and allele distribution of rs1719134 loci in the Ningxia Haiyuan region: the AA genotype of the case group was 27.9%, the AG genotype was 63%, the GG genotype was 9.1%, the AA genotype was 17.9% and the AG genotype was 71.1% in the control group. The GG genotype was 11.1%. using SPSS software for the test. The results showed that the distribution was in the case group and the control group. The statistical difference (P=0.027, OR=1.777 (1.066-2.964)); the A allele in the case group was 59.4%, the G allele was 40.6%, the A allele in the control group was 40.6%, and the G allele was 59.4%. using SPSS software for chi square test. The results showed that there was no statistical difference between the case group and the control group (P0.05).
The correlation analysis between the rs1130371 locus of 2MIP-1 a gene and the genetic susceptibility to tuberculosis: 100 cases of random selected case group and control group were sequenced. The results showed that there was no significant difference in the distribution of CT genotype and allele C and T in case control samples (P0.05). The total sample was found to have no TT genotype in the total sample.
3 the linkage disequilibrium analysis of MIP-1 alpha gene rs1130371 and rs1719134 was carried out with SHE SIS software, D 'value was 0.209, and R2 value was 0.003, indicating that the linkage imbalance of the two SNP loci was not close.
4 MIP-1 alpha gene rs1130371, rs1719134 and RANTES IN1.1 loci, 403 loci, and 28 loci of each genotype were analyzed with SHE SIS software for linkage disequilibrium, D 'value was 0.8, indicating that the linkage disequilibrium between the MIP-1 a gene and RANTES gene SNP loci was not close.
Conclusion 1MIP-1 alpha gene rs1719134 (A/G) is associated with the incidence of tuberculosis in the samples of Ningxia Haiyuan region, and its wild type AA genotype may be associated with the incidence of tuberculosis in the Haiyuan region of Ningxia.
The 2MIP-1 alpha gene rs1130371 (C/T) was only CC, CT two genotypes in 200 cases, and no TT genotype.CC was found. The distribution of CT genotypes was not statistically different in the case control group.
【学位授予单位】：宁夏医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R392

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