MIP-1α基因多態(tài)性與寧夏海原地區(qū)結核病的關聯研究
發(fā)布時間：2018-07-27 17:05
【摘要】：目的CC亞家族趨化因子巨噬細胞炎性蛋白-1α(macrophage inflammatory protein1-α，MIP-1α,CCL-3)在臨床水平與疾病關聯的研究也越來越受重視，在基因水平研究MIP-1α與疾病的預防、發(fā)生、發(fā)展和預后的判斷也是越來越受到眾多醫(yī)學科學工作者的關注。MIP-1α對巨噬細胞、單核細胞均有趨化活性，并且能誘導產生炎癥細胞因子，從而可以影響肉芽腫的發(fā)生和發(fā)展。MIP-1α基因的單核苷酸多態(tài)性（SNP）與疾病的相關性也逐步被人們所認識。本課題通過對MIP-1α基因rs1130371（C/T）、rs1719134（A/G）兩個多態(tài)性位點與結核病的關聯性研究來探討其與寧夏海原地區(qū)結核病遺傳易感性的關聯。 方法本研究采用以醫(yī)院為基礎的病例-對照研究設計，選擇寧夏海原地區(qū)154例臨床確診為結核病的病例組，，平均年齡（43.41±19.65），男女比例為79:75，選取與其性別年齡相匹配的寧夏海原地區(qū)的190例健康人群作為對照組，平均年齡在（43.11±15.90），男女比例為91:99。用聚合酶鏈反應-限制性片段長度多態(tài)性分析（PCR-RFLP）對rs1719134(A/G)位點進行基因分型；隨機選取各100例病例和對照樣本，平均年齡分別為43.36±22.36（病例組）和42.35±21.97（對照組），男女比例分別為57:43和59:41，用測序的方法對rs1130371(C/T)進行基因分型。用SPSS11.5統(tǒng)計學軟件分別計算其基因型、等位基因頻率，并進行卡方檢驗；同時用SHE sis軟件對2個SNP位點進行連鎖不平衡分析。對MIP-1α基因rs1719134和RANTES IN1.1位點、403位點、28位點用SHEsis軟件進行連鎖不平衡分析。 結果1MIP-1α基因rs1719134位點與結核病的遺傳易感性的相關性分析結果： 1.1寧夏海原地區(qū)樣本rs1719134位點基因型和等位基因分布：病例組AA基因型為27.9%，AG基因型為63.0%，GG基因型為9.1%，對照組中AA基因型為17.9%，AG基因型為71.1%，GG基因型為11.1%。用SPSS軟件進行卡方檢驗，結果顯示其分布在病例組和對照組中有統(tǒng)計學差異（P=0.027,OR=1.777（1.066-2.964））；病例組中A等位基因為59.4%，G等位基因為40.6%，對照組中A等位基因為40.6%，G等位基因為59.4%。用SPSS軟件進行卡方檢驗，結果顯示其分布在病例組和對照組中無統(tǒng)計學差異（P0.05）。 2MIP-1α基因rs1130371位點與結核病的遺傳易感性的相關性分析結果：隨機選擇病例組和對照組各100例進行測序分析，結果顯示CC,CT基因型和等位基因C,T在病例對照樣本中分布無顯著性差異（P0.05），本實驗發(fā)現總樣本200例均無TT基因型。 3用SHE sis軟件對MIP-1α基因rs1130371和rs1719134進行連鎖不平衡分析，D’值為0.209，r2值為0.003，說明這兩個SNP位點連鎖不平衡關系不緊密。 4對MIP-1α基因rs1130371,rs1719134和RANTES IN1.1位點，403位點，28位點各基因型用SHE sis軟件進行連鎖不平衡分析，D’值均0.8，表明MIP-1α基因和RANTES基因SNP位點連鎖不平衡關系不緊密。 結論1MIP-1α基因rs1719134（A/G）與寧夏海原地區(qū)樣本中結核病的發(fā)病有一定的關聯性，其野生型AA基因型可能和寧夏海原地區(qū)結核病發(fā)病有關聯。 2MIP-1α基因rs1130371（C/T）在200例樣本中只有CC,CT兩種基因型，沒有發(fā)現TT基因型。CC，CT基因型的分布在病例對照組中分布無統(tǒng)計學差異。
[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.
【學位授予單位】：寧夏醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R392
本文編號：2148537
[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.
【學位授予單位】：寧夏醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R392
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