本文選題：強(qiáng)直性脊柱炎 + DEFB4　； 參考：《安徽醫(yī)科大學(xué)》2015年碩士論文

【摘要】：目的1.探討β-防御素(DEFB4)基因拷貝數(shù)變異(Copy Number Variation,CNV)與強(qiáng)直性脊柱炎(Ankylosing Spondylitis,AS)遺傳易感性之間的關(guān)聯(lián)性;2.探討基因CNV是否會(huì)影響疾病的嚴(yán)重程度,同時(shí)研究與基因CNV在疾病發(fā)生發(fā)展進(jìn)程中相互影響的環(huán)境因素,為進(jìn)一步探索AS的發(fā)病原因,闡明AS的發(fā)病機(jī)制提供重要線索和依據(jù)。方法1.2011~2014年,收集安徽醫(yī)科大學(xué)第一附屬醫(yī)院風(fēng)濕免疫科門(mén)診確診的AS患者作為病例組,同時(shí)期按性別、年齡成組匹配,來(lái)安徽醫(yī)科大學(xué)第一附屬醫(yī)院體檢中心體檢的健康者為對(duì)照組,采用面對(duì)面問(wèn)卷調(diào)查法,用課題組自行設(shè)計(jì)的調(diào)查問(wèn)卷,收集患者和對(duì)照者的人口學(xué)資料:年齡、性別、文化水平、個(gè)人的行為習(xí)慣(吸煙、飲酒等)和飲食偏好,以及患者的臨床資料:病程、癥狀持續(xù)時(shí)間、BASDAI疾病活動(dòng)指數(shù)和BASFI功能指數(shù);實(shí)驗(yàn)室血清學(xué)指標(biāo):血沉、C反應(yīng)蛋白和HLA-B27等。在調(diào)查的同時(shí)采集患者和對(duì)照者的5ml外周血。2.DNA提取采用修改后的鹽析法,選取具有高度重復(fù)區(qū)域的兩個(gè)DEFB4基因片段(DEFB4_1和DEFB4_2),拷貝數(shù)的檢測(cè)采用Accu CopyTM法。3.采用病例對(duì)照以及單純病例研究設(shè)計(jì),分析比較DEFB4基因中CNV在AS患者和對(duì)照者中的差異,采用logistic回歸模型分析基因CNV與疾病、疾病的嚴(yán)重程度間的關(guān)聯(lián)性,用單純病例研究方法分析CNV與環(huán)境的交互作用。4.數(shù)據(jù)錄入軟件為Epidata3.1,采用雙人錄入并進(jìn)行一致性檢驗(yàn),數(shù)據(jù)分析采用SPSS19.0統(tǒng)計(jì)軟件實(shí)現(xiàn),P0.05差異有統(tǒng)計(jì)學(xué)意義。結(jié)果1.共納入806例研究對(duì)象,病例組405人,男性338人,平均年齡為27.91±8.93歲,中位病程為2.08年,HLA-B27陽(yáng)性率為64%;對(duì)照組401人,男性324人,平均年齡為26.89±7.12歲。兩組研究對(duì)象在性別(χ2=1.13,P=0.288)和年齡(t=1.77,P=0.076)上差異無(wú)統(tǒng)計(jì)學(xué)意義。2.DEFB4基因拷貝數(shù)的分布:AS患者,基因拷貝數(shù)范圍為1~8,DEFB4_1主要為2~4拷貝,DEFB4_2主要為2~5拷貝。對(duì)照組拷貝數(shù)范圍和病例組相同,DEFB4_1和DEFB4_2最多的拷貝均為3拷貝,分別占34.34%和27.14%。DEFB4_1(Z=0.63,P=0.528)和DEFB4_2(Z=1.27,P=0.111)拷貝數(shù)分布在病例組和對(duì)照組中差異無(wú)統(tǒng)計(jì)學(xué)意義。3.以3拷貝為界分兩組分析,DEFB4_2拷貝數(shù)在病例組和對(duì)照組中的分布差異有統(tǒng)計(jì)學(xué)意義(χ2=4.49,P=0.034),高拷貝數(shù)組(≥4)人群是低拷貝數(shù)組(≤3)人群可能患AS風(fēng)險(xiǎn)的0.74倍,95%CI(0.56,0.98)。進(jìn)一步分為三組:低拷貝數(shù)組(≤2),中拷貝數(shù)組(3),高拷貝數(shù)組(≥4),病例組和對(duì)照組拷貝數(shù)分布差異有統(tǒng)計(jì)學(xué)意義,χ2=8.68,P=0.013;與3拷貝數(shù)組比較,低拷貝數(shù)組和高拷貝數(shù)組人群分別是中拷貝數(shù)組人群可能患AS風(fēng)險(xiǎn)的0.68和0.62倍,但調(diào)整年齡和性別后,低拷貝數(shù)組與中拷貝數(shù)組比OR=0.69,95%CI(0.47,1.03),P=0.067,降低患AS風(fēng)險(xiǎn)的可能性無(wú)統(tǒng)計(jì)學(xué)意義。4.DEFB4_1和DEFB4_2拷貝數(shù)的增加是疾病嚴(yán)重度(BASDAI)增加的保護(hù)因素,OR,95%CI分別為0.71(0.56,0.90)和0.75(0.60,0.94),調(diào)整年齡、性別、病程之后,影響改變不大。未發(fā)現(xiàn)DEFB4基因CNV與身體功能(BASFI)的關(guān)聯(lián)性。5.DEFB4_1:食鹽口味中等的病人與食鹽口味輕的病人相比,基因×環(huán)境交互作用OR=0.51,95%CI(0.28,0.94),P=0.032,其他環(huán)境因素并未發(fā)現(xiàn)與基因的交互作用。DEFB4_2未發(fā)現(xiàn)拷貝數(shù)變異與環(huán)境的交互作用。結(jié)論DEFB4基因高拷貝數(shù)(≥4)是AS發(fā)病的保護(hù)因素,并且獨(dú)立于年齡和性別;基因CNV的拷貝數(shù)增加是獨(dú)立于年齡、性別和病程對(duì)疾病嚴(yán)重度增加的保護(hù)因素,但未發(fā)現(xiàn)基因CNV的增加與患者身體功能狀況的關(guān)聯(lián)性;基因環(huán)境交互作用分析提示,飲食口味可能與DEFB4基因拷貝數(shù)變異共同影響患AS的風(fēng)險(xiǎn)。
[Abstract]:Objective 1. to explore the correlation between the genetic susceptibility of Copy Number Variation (DEFB4) gene copy number variation (CNV) and ankylosing spondylitis (Ankylosing Spondylitis, AS), and 2. to explore whether the gene CNV will affect the severity of the disease and study the environmental factors that interact with the co gene CNV in the progression of the disease, In order to further explore the causes of AS, clarify the pathogenesis of AS, provide important clues and basis. Method 1.2011~2014, collected AS patients in the Department of Rheumatology of the First Affiliated Hospital of Medical University Of Anhui as case group, and matched by sex and age group at the same time, to come to the physical examination center of the First Affiliated Hospital of Medical University Of Anhui for physical examination. In the control group, we used a face-to-face questionnaire to collect the demographic data of patients and controls: age, sex, cultural level, personal behavior habits (smoking, drinking, etc.) and dietary preference, and the clinical data of patients: duration of disease, duration of symptoms, and BASDAI disease activity index. And BASFI function index; laboratory serological index: erythrocyte sedimentation, C reactive protein and HLA-B27. The 5ml peripheral blood.2.DNA extraction of patients and controls was collected by modified salting out method, and two DEFB4 gene fragments (DEFB4_1 and DEFB4_2) with high repetition area were selected, and the detection of copy number was carried out by Accu CopyTM method.3. mining Use case control and simple case study design, analyze and compare the difference of CNV in AS patients and controls in DEFB4 gene, use logistic regression model to analyze the correlation between gene CNV and disease, the severity of disease, and analyze the interaction of CNV and environment by simple case study method,.4. data entry software is Epidata3.1. The data analysis was realized with SPSS19.0 statistical software, and the difference of P0.05 was statistically significant. Results 1. a total of 806 subjects were included in the study. The case group was 405, male 338, the average age was 27.91 + 8.93, the median course was 2.08 years and the HLA-B27 positive rate was 64%; the control group was 401, 324 men and average age. There was no statistically significant difference in the distribution of.2.DEFB4 genes in sex (x 2=1.13, P=0.288) and age (t=1.77, P=0.076) in two groups of subjects: AS patients, 1~8, DEFB4_1 mainly 2~4 copies, DEFB4_2 mainly 2~5 copy, and the same number of copies of the control group as the case group, DEFB4_1, and cases. The most copies of the copies were 3 copies, which accounted for 34.34% and 27.14%.DEFB4_1 (Z=0.63, P=0.528) and DEFB4_2 (Z=1.27, P=0.111) copy number distribution in the case group and the control group with no statistically significant difference.3. with 3 copies as the two groups. The distribution difference of DEFB4_2 in the case group and the contrast group was statistically significant (x 2=4.49, P=0.034). High copy array (> 4) population is low copy array (less than 3) people may suffer 0.74 times the risk of AS, 95%CI (0.56,0.98). Further divided into three groups: low copy array (< < 2), medium copy array (3), high copy array (> 4). The difference of copy number distribution in case group and control group is statistically significant, X 2=8.68, P=0.013; compared with 3 copy array, low copy Array and high copy array groups are 0.68 and 0.62 times the risk of AS, respectively, but after adjusting age and sex, low copy array and medium copy array are more than OR=0.69,95%CI (0.47,1.03), P=0.067, and the possibility of reducing AS risk is not statistically significant.4.DEFB4_1 and DEFB4_2 copy number increase is disease severity (BAS). DAI) increased protective factors, OR, 95%CI were 0.71 (0.56,0.90) and 0.75 (0.60,0.94), adjusting age, sex, and course of disease, the influence changed little. No DEFB4 gene CNV and body function (BASFI) associated.5.DEFB4_1: salt taste moderate patients were compared with salt flavored patients, gene * environmental interaction OR=0.51,95%CI (0) .28,0.94), P=0.032, other environmental factors did not find the interaction with the gene,.DEFB4_2 did not find the interaction between the copy number variation and the environment. Conclusion the high copy number of the DEFB4 gene (> 4) is a protective factor for the pathogenesis of AS, and is independent of age and sex; the increase of the copy number of the gene CNV is independent of age, sex and course of disease are serious to the disease. The degree of protection was increased, but the association between the increase of gene CNV and the physical function of the patient was not found, and the genetic environmental interaction analysis suggested that the dietary taste may affect the risk of AS with the variation of the copy number of the DEFB4 gene.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R593.23

【共引文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前2條

1 李桂興;IL-33及受體ST2調(diào)控的Th2免疫應(yīng)答與強(qiáng)直性脊柱炎的關(guān)聯(lián)性研究[D];安徽醫(yī)科大學(xué);2013年

2 陳庭瑞;強(qiáng)直性脊柱炎患者脊柱運(yùn)動(dòng)能力的研究[D];南方醫(yī)科大學(xué);2013年

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本文編號(hào)：1968318