内蒙古地区蒙、汉民族人群支气管哮喘与解整合素—金属蛋白酶33基因多态性的相关性研究

发布时间：2018-07-05 09:26

本文选题：ADAM33 + 哮喘　；参考：《武汉大学》2016年博士论文

【摘要】：第一部分解整合素-金属蛋白酶33基因多态性与内蒙古地区蒙、汉民族人群哮喘的相关性研究目的：了解内蒙古地区蒙、汉民族支气管哮喘患者发病的一般临床资料,研究蒙、汉民族支气管哮喘人群ADAM33基因T1、T2、V4、S2位点不同基因型及等位基因频率的分布,探讨ADAM33基因多态性与支气管哮喘的关系。方法：采用一般情况调查表、临床检查等,收集支气管哮喘患者发病的一般临床资料,选用限制性片段长度多态性(PCR-RFLP)方法对汉族哮喘患者130例、蒙古族哮喘患者118例进行ADAM33基因多态性的检测,并分别与134例健康汉族和122例健康蒙族进行比较,筛选有意义基因。结果：内蒙古地区蒙、汉民族支气管哮喘患者的体重指数、吸烟者(%)、FEV1%预计值、FEV1/FVC在哮喘组与对照组间比较,差异有统计学意义。蒙、汉民族人群均可检出T1、T2、V4、S2位点的3种基因型,健康汉族与健康蒙古族各位点基因型及等位基因频率比较,差异无统计学意义(p0.05)。对汉族支气管哮喘组与对照组T1位点基因型、等位基因频率进行比较, AA、AG型差异有统计学意义(P0.05),OR值(95%CI)分别为2.089(1.159-3.765)、0.449(0.242-0.831),等位基因G的OR值(95%CI)为0.557(0.329-0.942)；对S2位点基因型、等位基因频率进行比较,CC、GC型差异有统计学意义(P0.05),0R值(95%CI)分别为0.573(0.349-0.941)、1.648(0.998-1.850),等位基因G的0R值(95%CI)为1.559(1.026-2.371)；对T2、V4位点基因型、等位基因频率进行比较,差异无统计学意义(p0.05)。对蒙古族支气管哮喘组与对照组T1位点基因型、等位基因频率进行比较,AA、AG型差异有统计学意义(P0.05),OR值(95%CI)分别2.295(1.200-4.391)、心.395(0.198-0.789),等位基因G的OR值(95% CI)为0.518(0.291-0.922)；对V4位点基因型、等位基因频率进行比较,GC、GG型差异有统计学意义(P0.05),OR值(95%CI)分别为心.363(0.179-0.736)、 2.555(1.463-4.462),等位基因G的OR值(95%CI)为1.715(1.190-2.473)：对S2位点基因型、等位基因频率进行比较,GC、GG型差异有统计学意义(P0.05),OR值(95%CI)分别为0.540(0.320-0.911)、1.802(1.063-3.055),等位基因G的OR值(95%CI)为1.603(1.028-2.500)；对T2位点基因型、等位基因频率进行比较,差异无统计学意义(p0.05)。即T2位点基因型及等位基因在蒙古族、汉族哮喘与对照组分别比较,差异均无统计学意义(P0.05)；而T1、S2位点基因型及等位基因在蒙古族、汉族哮喘与对照组分别比较,差异均有统计学意义(P0.05)；V4位点基因型及等位基因在汉族哮喘与对照组比较差异无统计学意义(P0.05),但在蒙古族哮喘患者中比较,差异有统计学意义。结论：肥胖者、吸烟者是哮喘的高危人群,ADAM33基因T1、S2位点多态性在中国内蒙古地区蒙、汉民族哮喘人群中可能均发挥作用,V4位点多态性仅在蒙古族哮喘人群中发挥作用,而T2位点多态性可能与内蒙古地区蒙、汉族哮喘人群无关。第二部分蒙古族支气管哮喘患者ADAM33基因多态性与疾病严重程度的相关性研究目的：研究内蒙古地区蒙古族人群ADAM33基因T1、T2、V4、S2位点不同基因型及等位基因频率的分布,探讨其不同位点基因型与支气管哮喘严重程度的相关性。方法：选用限制性片段长度多态性(PCR-RFLP)方法对蒙古族哮喘患者180例进行ADAM33基因多态性的检测,与186例健康蒙族进行比较,筛选有意义基因。根据病情将哮喘组分为轻度(间歇性-持续性)哮喘组、中度持续性哮喘组、重度持续性哮喘组,其中轻度组83例,中度组47例、重度组50例,比较不同程度组基因型分布差异,检测所有入选者肺功能、外周血嗜酸性粒细胞及IgE,对不同程度组基因型分布差异有统计学意义的基因各基因型进行比较,分析其相关性。结果：ADAM33基因T1位点AA、AG基因型,在哮喘组与对照组比较差异有显著性(x2分别为8.810、8.294,均P0.05),OR值为1.983、0.500,G等位基因0R值为0.580；S2位点CC基因型,两组比较差异有统计学意义(x2=4.277、P0.05),等位基因G的OR值为1.423；V4位点GC、GG基因型,两组比较差异有统计学意义(x2分别为7.880、10.313,均P0.05),OR值为0.459、2.130,等位基因G的OR值为1.496。T2位点各基因型在哮喘组和对照组中分布差异无统计学意义(x2分别为1.218、0.248、1.287,均P0.05)。V4位点各基因型在轻、中、重度组分布频率差异有统计学意义(x2=16.049,P0.05),且对各基因型的FEVI、IgE进行比较,差异有统计学意义(P0.05),对各基因型的嗜酸性粒细胞进行比较,差异无统计学意义(PO.05)。结论：ADAM33基因T1、V4、S2位点多态性在中国内蒙古地区蒙古族哮喘人群中可能发挥作用,而T2位点多态性可能与内蒙古地区蒙古族哮喘人群无关。V4位点基因多态性可能与哮喘严重程度有关,可与肺功能、IgE联合检测,作为评估支气管哮喘严重程度的潜在指标。
[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.
【学位授予单位】：武汉大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R562.25

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