本文關(guān)鍵詞： 白介素-25 變應(yīng)性鼻炎 固有免疫 單核苷酸多態(tài)性 遺傳學(xué)關(guān)聯(lián)研究　出處：《南京醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:探討白介素-25(interleukin-25,IL-25)基因序列單核苷酸多態(tài)性(single nucleotide polymorphisms,SNPs)與蘇皖漢族人群塵螨致敏的持續(xù)性變應(yīng)性鼻炎(persistent allergic rhinitis,PER)的遺傳關(guān)聯(lián)性。方法:采取病例-對照研究,病例組納入塵螨致敏的PER患者525例(年齡2～64歲,中位數(shù)24歲),對照組納入健康志愿者611例(年齡2～69歲,中位數(shù)25歲)。收集相關(guān)臨床資料,并進(jìn)行體格檢查及血清總IgE、特異性IgE測定,提取DNA。根據(jù)HapMap數(shù)據(jù)庫內(nèi)中國北京漢族人群數(shù)據(jù),基于連鎖不平衡和功能位點的預(yù)測相結(jié)合的策略,按照最小等位基因頻率(MAF)0.05和r20.8標(biāo)準(zhǔn),結(jié)合文獻(xiàn)參考,篩選IL-25基因tag SNPs位點rs10137082、rs7145551和rs3811178,進(jìn)行TaqMan基因分型。使用Logistic回歸模型分析IL-25基因SNPs與PER發(fā)病風(fēng)險的關(guān)系,HAPSTATA3.0軟件分析單體型,廣義多因子降維法(GMDR)分析基因與基因之間交互作用。結(jié)果:分析人群基礎(chǔ)數(shù)據(jù)顯示,病例組與對照組的年齡、性別分布均無統(tǒng)計學(xué)差異(P0.05),病例組和對照組血清總IgE水平分別為211.70(97.36,454.74)kU/L 和 33.20(15.58,62.26)kU/L,差異具有統(tǒng)計學(xué)意義(P0.01)。在 Logistic回歸模型中矯正年齡、性別等混雜因素后發(fā)現(xiàn),IL-25基因3個SNPs與PER之間均無顯著性關(guān)聯(lián)(P0.05)。進(jìn)一步分層分析發(fā)現(xiàn)在年齡25歲人群中,IL-25基因rs10137082在突變純合子(TT基因型)可增加PER易感性(P=0.036,OR=4.056,95%CI 1.097-15.001)。GMDR 分析未見 IL-25 基因 SNPs 位點之間存在交互作用,同時單體型分析亦未發(fā)現(xiàn)IL-25基因SNPs位點存在與PER相關(guān)的單體型。結(jié)論:IL-25 基因 SNPs 位點 rs10137082、rs7145551 和 rs3811178 與蘇皖漢族人群塵螨致敏的PER無明顯的遺傳學(xué)關(guān)聯(lián)。年齡可能對rs10137082多態(tài)性位點與PER的相關(guān)性有一定影響,有關(guān)機(jī)制有待于進(jìn)一步深入研究。
[Abstract]:Objective: to study interleukin-25 interleukin-25. The single nucleotide polymorphisms of IL-25 gene were identified as single nucleotide polymorphisms. SNPs) and persistent allergic rhinitis (allergic rhinitis) sensitized by dust mites in Jiangsu and Anhui Han population. Methods: a case-control study was conducted in 525 patients with PER sensitized to dust mites (age 2: 64 years, median 24 years). In the control group, 611 healthy volunteers (age 2 to 69 years, median 25 years old) were enrolled in the study. The clinical data were collected, and the physical examination, serum total IgE and specific IgE were performed. Based on the data of Han population in Beijing, China, the strategy of combining linkage disequilibrium and functional locus prediction was used to extract DNA.According to the data of Chinese Han population in HapMap database. According to the criteria of minimum allele frequency and r20.8, tag SNPs site rs10137082 of IL-25 gene was screened according to the reference of literature. Rs7145551 and rs3811178. TaqMan genotyping was performed and Logistic regression model was used to analyze the relationship between IL-25 gene SNPs and PER risk. HAPSTATA3.0 software was used to analyze haplotype and generalized multi-factor dimensionality reduction method (GMDR) to analyze the interaction between gene and gene. Results: the basic data of population were analyzed. There was no significant difference in age and sex distribution between the case group and the control group (P 0.05). The total serum IgE levels in the case group and the control group were 211.70 鹵97.36 respectively. 454.74 kU / L and 33.20 / 15.58 / L 62.26kU / L. The difference was statistically significant (P 0.01). After correction of age, sex and other confounding factors in Logistic regression model, we found. There was no significant correlation between three SNPs and PER of IL-25 gene. IL-25 gene rs10137082 in homozygote TT genotype could increase the susceptibility of PER. There was no interaction between SNPs loci of IL-25 gene in 95 CI 1.097-15.001GMDR analysis. At the same time, haplotype analysis showed that there was no haplotype associated with PER at the SNPs locus of IL-25 gene. Rs7145551 and rs3811178. There was no significant genetic association with PER sensitized to dust mite in Jiangsu and Anhui Han population. Age may have some influence on the association between rs10137082 polymorphism and PER. The mechanism remains to be further studied.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R765.21

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