本文選題：ADAM33 + 哮喘　； 參考：《武漢大學(xué)》2016年博士論文

【摘要】：第一部分解整合素-金屬蛋白酶33基因多態(tài)性與內(nèi)蒙古地區(qū)蒙、漢民族人群哮喘的相關(guān)性研究目的：了解內(nèi)蒙古地區(qū)蒙、漢民族支氣管哮喘患者發(fā)病的一般臨床資料,研究蒙、漢民族支氣管哮喘人群ADAM33基因T1、T2、V4、S2位點(diǎn)不同基因型及等位基因頻率的分布,探討ADAM33基因多態(tài)性與支氣管哮喘的關(guān)系。方法：采用一般情況調(diào)查表、臨床檢查等,收集支氣管哮喘患者發(fā)病的一般臨床資料,選用限制性片段長(zhǎng)度多態(tài)性(PCR-RFLP)方法對(duì)漢族哮喘患者130例、蒙古族哮喘患者118例進(jìn)行ADAM33基因多態(tài)性的檢測(cè),并分別與134例健康漢族和122例健康蒙族進(jìn)行比較,篩選有意義基因。結(jié)果：內(nèi)蒙古地區(qū)蒙、漢民族支氣管哮喘患者的體重指數(shù)、吸煙者(%)、FEV1%預(yù)計(jì)值、FEV1/FVC在哮喘組與對(duì)照組間比較,差異有統(tǒng)計(jì)學(xué)意義。蒙、漢民族人群均可檢出T1、T2、V4、S2位點(diǎn)的3種基因型,健康漢族與健康蒙古族各位點(diǎn)基因型及等位基因頻率比較,差異無統(tǒng)計(jì)學(xué)意義(p0.05)。對(duì)漢族支氣管哮喘組與對(duì)照組T1位點(diǎn)基因型、等位基因頻率進(jìn)行比較, AA、AG型差異有統(tǒng)計(jì)學(xué)意義(P0.05),OR值(95%CI)分別為2.089(1.159-3.765)、0.449(0.242-0.831),等位基因G的OR值(95%CI)為0.557(0.329-0.942)；對(duì)S2位點(diǎn)基因型、等位基因頻率進(jìn)行比較,CC、GC型差異有統(tǒng)計(jì)學(xué)意義(P0.05),0R值(95%CI)分別為0.573(0.349-0.941)、1.648(0.998-1.850),等位基因G的0R值(95%CI)為1.559(1.026-2.371)；對(duì)T2、V4位點(diǎn)基因型、等位基因頻率進(jìn)行比較,差異無統(tǒng)計(jì)學(xué)意義(p0.05)。對(duì)蒙古族支氣管哮喘組與對(duì)照組T1位點(diǎn)基因型、等位基因頻率進(jìn)行比較,AA、AG型差異有統(tǒng)計(jì)學(xué)意義(P0.05),OR值(95%CI)分別2.295(1.200-4.391)、 心.395(0.198-0.789),等位基因G的OR值(95% CI)為0.518(0.291-0.922)；對(duì)V4位點(diǎn)基因型、等位基因頻率進(jìn)行比較,GC、GG型差異有統(tǒng)計(jì)學(xué)意義(P0.05),OR值(95%CI)分別為心.363(0.179-0.736)、 2.555(1.463-4.462),等位基因G的OR值(95%CI)為1.715(1.190-2.473)：對(duì)S2位點(diǎn)基因型、等位基因頻率進(jìn)行比較,GC、GG型差異有統(tǒng)計(jì)學(xué)意義(P0.05),OR值(95%CI)分別為0.540(0.320-0.911)、1.802(1.063-3.055),等位基因G的OR值(95%CI)為1.603(1.028-2.500)；對(duì)T2位點(diǎn)基因型、等位基因頻率進(jìn)行比較,差異無統(tǒng)計(jì)學(xué)意義(p0.05)。即T2位點(diǎn)基因型及等位基因在蒙古族、漢族哮喘與對(duì)照組分別比較,差異均無統(tǒng)計(jì)學(xué)意義(P0.05)；而T1、S2位點(diǎn)基因型及等位基因在蒙古族、漢族哮喘與對(duì)照組分別比較,差異均有統(tǒng)計(jì)學(xué)意義(P0.05)；V4位點(diǎn)基因型及等位基因在漢族哮喘與對(duì)照組比較差異無統(tǒng)計(jì)學(xué)意義(P0.05),但在蒙古族哮喘患者中比較,差異有統(tǒng)計(jì)學(xué)意義。結(jié)論：肥胖者、吸煙者是哮喘的高危人群,ADAM33基因T1、S2位點(diǎn)多態(tài)性在中國內(nèi)蒙古地區(qū)蒙、漢民族哮喘人群中可能均發(fā)揮作用,V4位點(diǎn)多態(tài)性僅在蒙古族哮喘人群中發(fā)揮作用,而T2位點(diǎn)多態(tài)性可能與內(nèi)蒙古地區(qū)蒙、漢族哮喘人群無關(guān)。第二部分蒙古族支氣管哮喘患者ADAM33基因多態(tài)性與疾病嚴(yán)重程度的相關(guān)性研究目的：研究?jī)?nèi)蒙古地區(qū)蒙古族人群ADAM33基因T1、T2、V4、S2位點(diǎn)不同基因型及等位基因頻率的分布,探討其不同位點(diǎn)基因型與支氣管哮喘嚴(yán)重程度的相關(guān)性。方法：選用限制性片段長(zhǎng)度多態(tài)性(PCR-RFLP)方法對(duì)蒙古族哮喘患者180例進(jìn)行ADAM33基因多態(tài)性的檢測(cè),與186例健康蒙族進(jìn)行比較,篩選有意義基因。根據(jù)病情將哮喘組分為輕度(間歇性-持續(xù)性)哮喘組、中度持續(xù)性哮喘組、重度持續(xù)性哮喘組,其中輕度組83例,中度組47例、重度組50例,比較不同程度組基因型分布差異,檢測(cè)所有入選者肺功能、外周血嗜酸性粒細(xì)胞及IgE,對(duì)不同程度組基因型分布差異有統(tǒng)計(jì)學(xué)意義的基因各基因型進(jìn)行比較,分析其相關(guān)性。結(jié)果：ADAM33基因T1位點(diǎn)AA、AG基因型,在哮喘組與對(duì)照組比較差異有顯著性(x2分別為8.810、8.294,均P0.05),OR值為1.983、0.500,G等位基因0R值為0.580；S2位點(diǎn)CC基因型,兩組比較差異有統(tǒng)計(jì)學(xué)意義(x2=4.277、P0.05),等位基因G的OR值為1.423；V4位點(diǎn)GC、GG基因型,兩組比較差異有統(tǒng)計(jì)學(xué)意義(x2分別為7.880、10.313,均P0.05),OR值為0.459、2.130,等位基因G的OR值為1.496。T2位點(diǎn)各基因型在哮喘組和對(duì)照組中分布差異無統(tǒng)計(jì)學(xué)意義(x2分別為1.218、0.248、1.287,均P0.05)。V4位點(diǎn)各基因型在輕、中、重度組分布頻率差異有統(tǒng)計(jì)學(xué)意義(x2=16.049,P0.05),且對(duì)各基因型的FEVI、IgE進(jìn)行比較,差異有統(tǒng)計(jì)學(xué)意義(P0.05),對(duì)各基因型的嗜酸性粒細(xì)胞進(jìn)行比較,差異無統(tǒng)計(jì)學(xué)意義(PO.05)。結(jié)論：ADAM33基因T1、V4、S2位點(diǎn)多態(tài)性在中國內(nèi)蒙古地區(qū)蒙古族哮喘人群中可能發(fā)揮作用,而T2位點(diǎn)多態(tài)性可能與內(nèi)蒙古地區(qū)蒙古族哮喘人群無關(guān)。V4位點(diǎn)基因多態(tài)性可能與哮喘嚴(yán)重程度有關(guān),可與肺功能、IgE聯(lián)合檢測(cè),作為評(píng)估支氣管哮喘嚴(yán)重程度的潛在指標(biāo)。
[Abstract]:The first analysis of the correlation between the polymorphism of the integrin metalloproteinase 33 gene and the asthma in Mongolian and Han people in Inner Mongolia. Objective: to understand the general clinical data of the pathogenesis of bronchial asthma in Mongolian and Han nationality in Inner Mongolia, and to study the different genotype of ADAM33 gene T1, T2, V4 and S2 loci in Mongolian and Han ethnic group. The distribution of allele frequency and the relationship between ADAM33 gene polymorphism and bronchial asthma. Methods: general situation questionnaire, clinical examination, general clinical data of patients with bronchial asthma were collected, 130 cases of Han asthma and 118 Mongolian asthma patients were selected by restrictive fragment length polymorphism (PCR-RFLP). The ADAM33 gene polymorphism was detected and compared with 134 healthy Han and 122 healthy Mongolian people. The results showed that the body mass index (BMI), smokers (%), FEV1% predicted value, and FEV1/FVC between asthma group and control group in Mongolian and Han nationality in Inner Mongolia area were statistically significant. There were 3 genotypes of T1, T2, V4 and S2 loci in the ethnic group. There was no significant difference in the genotype and allele frequencies between the healthy Han and the healthy Mongolian people (P0.05). The genotype and allele frequencies of the T1 loci in the bronchial asthma group and the control group were compared, and the differences in AA and AG were statistically significant (P0.05), OR. (P0.05), OR, and OR. The value (95%CI) was 2.089 (1.159-3.765), 0.449 (0.242-0.831), and the OR value of the allele G (95%CI) was 0.557 (0.329-0.942), and the allele frequencies of the S2 loci were compared, the CC and GC types were statistically significant (P0.05), and the 0R values were 1.559 (1.) and 1.559 (1.). 026-2.371); there was no significant difference in the allele frequencies of T2, V4 loci and allele frequencies (P0.05). Compared to the genotype and allele frequencies of the T1 loci in the Mongolian bronchial asthma group and the control group, the AA, AG type differences were statistically significant (P0.05), the OR value (95%CI) was 2.295 (1.200-4.391), the cardiac.395 (P0.05), and the allele group. The OR value of G (95% CI) was 0.518 (0.291-0.922); the genotype of V4 loci and allele frequencies were compared, GC, GG type differences were statistically significant (P0.05), OR values (95%CI) were cardiac.363 (0.179-0.736), 2.555, respectively: allele genotype, allele frequency ratio was compared. The difference between GC and GG was statistically significant (P0.05), and the OR value (95%CI) was 0.540 (0.320-0.911), 1.802 (1.063-3.055), and the OR value of the allele G (95%CI) was 1.603 (1.028-2.500), and the allele frequency of the allele and allele of the allele was not statistically significant. Compared with the control group, the difference was not statistically significant (P0.05), while T1, S2 genotype and allele in Mongolian, Han asthma and control group were compared with the control group, the difference was statistically significant (P0.05), and there was no statistical difference between the genotype and allele of the V4 locus and the allele in the Han asthma and the control group (P0.05), but in the Mongolian nationality. The difference has statistical significance. Conclusion: obese people, smokers are high-risk groups of asthma, ADAM33 gene T1, S2 polymorphism may play a role in Mongolian and Han ethnic asthma population in Inner Mongolia area of China, V4 locus polymorphism only plays a role in Mongolian wheezing population, and the polymorphism of T2 loci may be in and within. The relationship between the ADAM33 gene polymorphism of the second Mongolian bronchial asthma and the severity of the disease was studied. The purpose of the study was to study the distribution of different genotype and allele frequencies of ADAM33 gene T1, T2, V4, S2 loci in Mongolian people of the Mongolian population in Inner Mongolia region, and to explore the genotypes and branches of the different loci. Method: the restriction fragment length polymorphism (PCR-RFLP) method was used to detect the polymorphism of ADAM33 gene in 180 Mongolian asthma patients, and compared with 186 healthy Mongolian people, the significant genes were selected. According to the condition, the asthma group was divided into mild (intermittent persistent) asthma group and moderate holding. In the continuous asthma group and severe persistent asthma group, 83 cases in the mild group, 47 in the moderate group and 50 in the severe group, compared the difference of genotype distribution in the different degree group. The lung function, the eosinophil and IgE in the peripheral blood were detected in all the selected subjects, and the genotypes of different genotypes were compared and analyzed. Results: the ADAM33 gene T1 locus AA and AG genotype were significantly different in the asthma group from the control group (x2 was 8.810,8.294, P0.05), OR value was 1.983,0.500, G allele 0R was 0.580, and the S2 locus allele, the two groups were statistically significant (1.423). GC, GG genotypes, the two groups were statistically significant (x2 was 7.880,10.313, P0.05), OR was 0.459,2.130, and the OR value of the allele G was 1.496.T2 loci in the asthma group and the control group with no statistical significance (X2 is 1.218,0.248,1.287, both) in the light, medium, and severe components. The difference in frequency of cloth was statistically significant (x2=16.049, P0.05), and the difference between FEVI and IgE was statistically significant (P0.05). There was no significant difference between the genotypes of eosinophils (PO.05). Conclusion: the polymorphism of ADAM33 gene T1, V4 and S2 loci was in the Mongolian asthma population in Inner Mongolia area of China. It may play a role, and the polymorphism of T2 loci may be related to the severity of asthma, which may be associated with the severity of asthma in the Mongolian asthma population in Inner Mongolia, and can be combined with lung function and IgE as a potential indicator for assessing the severity of bronchial asthma.
【學(xué)位授予單位】：武漢大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R562.25

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