湖南省哮喘儿童ORMDL3基因多态性分析及与OPN、TGF-β1水平相关性探讨

发布时间：2018-07-05 01:30

本文选题：儿童 + 哮喘　；参考：《中南大学》2012年硕士论文

【摘要】：目的：研究中国湖南省汉族儿童ORMDL3基因的单核苷酸多态性(single nuclcotidc polymorphism, SNP)的分布情况,并分析其与特应性体质及哮喘易感性之间的关系；探讨ORMDL3基因的SNP与血清骨桥蛋白(osteopontin, OPN)(?)口转化生长因子p1(媲nsforming growth factor-β1, TGF-β1)含量变化的相关性。方法：收集2010年12月至2011年10月在湖南省儿童医院住院的0-5岁哮喘患儿98例设立为哮喘组,并根据3代直系亲属有无过敏性疾病将哮喘组分为伴特应质和无特应质两组,同时收集非哮喘儿童30名作为对照组,采用DNA直接测序法对两组儿童ORMDL3基因rs7216389位点的SNP进行测定；采用酶联免疫吸附法(enzyme-linked imunosorbent assay, ELISA)测定哮喘组及对照组儿童血清中OPN和TGF-β1的含量；用相关分析对ORMDL3基因多态性与血清中OPN和TGF-β1的含量变化进行相关分析。结果：(1)ORMDL3基因多态性分析：ORMDL3基因rs7216389位点存在多态性,基因型有AA、AG和GG三种类型。哮喘组AA、AG和GG三种基因型的频率分别是68.4%、23.5%、8.1%,A、G等位基因频率分别为80.1%、19.9%；对照组三种基因型的频率分别是60.0%26.7%和13.3%,A、G等位基因频率分别为73.3%、26.7%。两组基因型及等位基因频率差异无统计学意义(χ2分别为0.994和1.248,P均0.05)。哮喘伴特应质组AA、AG和GG三种基因型的频率分别是71.0%、22.6%和6.4%,等位基因A、G的频率分别为82.3%、17.7%；哮喘无特应质组AA、AG和GG三种基因型的频率分别是63.9%、25.0%和11.1%,等位基因A、G的频率分别为76.4%、23.6%。两组基因型及等位基因频率差异无统计学意义(χ2分别为0.829和0.984,P均0.05)。(2)血清中OPN、TGF-β1含量比较：哮喘组和对照组的血清OPN分别为18.68±4.94ng/mL和13.53±3.55ng/mL,哮喘组较对照组明显增加,差异有统计学意义(t=5.296,P0.05)；哮喘伴特应质组及哮喘无特应质组的OPN含量分别为18.71±5.53ng/mL和18.63±3.81ng/mL,与对照组比较明显增加,差异有统计学意义(P0.05)；哮喘伴特应质组与哮喘无特应质组比较,OPN含量差异无统计学意义(P0.05)；哮喘组与对照组TGF-β1含量分别为69.86±31.76pg/mL和47.06±23.76pg/mL,哮喘组TGF-β1含量与对照组比较显著增加,差异有统计学意义(t=3.630,P0.05)；哮喘伴特应质组与哮喘无特应质组TGF-β1含量分别为79.03±32.96pg/mL和54.08±22.29pg/mL,哮喘伴特应质组与哮喘无特应质组及对照组比较显著增高,差异有统计学意义(P0.05),哮喘无特应质组和对照组比较TGF-β1含量差异无统计学意义(P0.05)；单因素方差分析显示不同组别的各基因型之间的OPN及TGF-β1含量差异均无统计学意义。(3)相关分析：血清OPN与TGF-β1含量在哮喘组中呈直线正相关,在哮喘伴特应质组和无特应质组中也呈直线正相关。结论：(1)我国湖南省汉族儿童ORMDL3基因rs7216389存在SNP,该位点的SNP与我国湖南省汉族儿童的哮喘易感性可能无明显关联；(2)ORMDL3基因的rs7216389位点可能不是影响我国湖南省汉族哮喘儿童的特应质的位点；(3)OPN、TGF-β1可能参与了哮喘的发生及发展过程,且两者呈直线正相关；(4)OPN、TGF-β1的表达可能不受ORMDL3基因rs72163896位点的SNP的影响。
[Abstract]:Objective: To study the distribution of single nuclcotidc polymorphism (SNP) of the ORMDL3 gene of the Han children in Hunan Province, and to analyze the relationship with the atopic constitution and the susceptibility to asthma, and to explore the SNP of the ORMDL3 gene and the serum osteopontin (osteopontin, OPN) (?) oral transforming growth factor P1 (comparable nsforming). Correlation of growth factor- beta 1, TGF- beta 1 content changes.
Methods: 98 cases of asthma in 0-5 year old asthmatic children hospitalized in Hunan Children's Hospital from December 2010 to October 2011 were set up as asthma group. According to the 3 generation of direct relatives, the asthma group was divided into groups of atopic and non atopic two, and 30 non asthmatic children were collected as control group, and two groups were treated by DNA direct sequencing. The SNP of the rs7216389 locus of the child ORMDL3 gene was measured and the content of OPN and TGF- beta 1 in the serum of the children of asthma and the control group was measured by enzyme-linked imunosorbent assay (ELISA), and the correlation analysis was used to analyze the correlation between the ORMDL3 gene polymorphism and the content of OPN and TGF- beta 1 in the serum.
Results: (1) ORMDL3 gene polymorphism analysis: the polymorphism of the ORMDL3 gene rs7216389 locus, the genotype of AA, AG and GG, the frequencies of the three genotypes of AA, AG and GG in the asthma group were 68.4%, 23.5%, 8.1%, A, and G alleles respectively 80.1% and 19.9% respectively. The frequencies of the three genotypes in the control group were 60.0%26.7% and 13.3%, respectively, respectively. Allele frequencies were 73.3% respectively, and there was no significant difference in genotype and allele frequency between 26.7%. two groups (0.994 and 1.248, P 0.05). The frequencies of AA, AG and GG genotype were 71%, 22.6% and 6.4%, and the allele A, G frequencies were 82.3%, 17.7%, AA, AG and GG in the asthma free group. The frequencies of the three genotypes were 63.9%, 25% and 11.1%, the allele A, the frequency of G were 76.4%, the genotype and allele frequencies of the 23.6%. two groups were not statistically significant (0.829 and 0.984, P 0.05 respectively). (2) the serum OPN and TGF- beta 1 content were compared: the serum OPN of the asthma group and the control group was 18.68 + 4.94ng/mL and 13.53 respectively. 3.55ng/mL, the asthma group was significantly higher than the control group, the difference was statistically significant (t=5.296, P0.05), and the OPN content in the asthma group and the asthma free group was 18.71 + 5.53ng/mL and 18.63 + 3.81ng/mL respectively, and the difference was significantly increased with the control group (P0.05), and the asthma accompanied the atopic group and the asthma without special stress. The difference of OPN content was not statistically significant (P0.05), the content of TGF- beta 1 in the asthma group and the control group was 69.86 + 31.76pg/mL and 47.06 + 23.76pg/mL respectively. The TGF- beta 1 content in the asthma group was significantly increased with the control group, the difference was statistically significant (t=3.630, P0.05), and the TGF- beta 1 content in the asthma combined with the atopic group and the asthma free group was 79., respectively. 03 + 32.96pg/mL and 54.08 + 22.29pg/mL, the asthma combined with atopic group was significantly higher than the non idiopathic asthma group and the control group, the difference was statistically significant (P0.05). There was no significant difference in the content of TGF- beta 1 in the non idiopathic asthma group and the control group (P0.05). The single factor difference analysis showed the OPN and T between the different genotypes of different groups. There was no significant difference in the content of GF- beta 1. (3) correlation analysis: the content of serum OPN and TGF- beta 1 was in linear positive correlation in asthma group, and was also in linear positive correlation in asthma with idiopathic group and non atopic group.
Conclusion: (1) the ORMDL3 gene rs7216389 of Han children in Hunan province exists SNP, and the SNP of this loci may have no obvious association with the susceptibility to asthma in Han children in Hunan province of China. (2) the loci of the ORMDL3 gene may not affect the atopic loci of the asthma children of Hunan Han, and (3) OPN, TGF- beta 1 may be involved in the asthma. There was a positive correlation between the occurrence and development of asthma and the two. (4) the expression of OPN and TGF- beta 1 may not be affected by the SNP of the rs72163896 locus of ORMDL3 gene.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R725.6

【参考文献】