研究背景:支氣管哮喘是一種常見的呼吸系統(tǒng)變態(tài)反應性疾病,是由免疫、遺傳、環(huán)境以及其他因素共同作用而引起的多基因遺傳病,遺傳度為70%～80%,哮喘發(fā)病呈現(xiàn)多因性和異質(zhì)性,并由不同的遺傳機制控制。迄今為止,哮喘的臨床預后仍然是不盡人意,因此,尋找哮喘的易感基因進而探索其發(fā)生的分子機制是防治哮喘的根本途徑。維生素D受體（VDR）是介導1,25（OH）₂D₃發(fā)揮生物效應的核內(nèi)生物大分子,為類固醇激素/甲狀腺激素受體超家族的成員。1,25（OH）₂D₃激素信號分子在靶細胞與VDR結合形成激素-受體復合物,該復合物作用于靶基因上的特定DNA序列。從而對結構基因的表達產(chǎn)生調(diào)節(jié)作用。因此,VDR在本質(zhì)上是一種配體依賴的核轉錄因子。它在維持機體鈣、磷代謝,調(diào)節(jié)細胞增殖、分化等方面起重要作用,此外研究還證實,VDR基因可以通過調(diào)節(jié)T細胞的發(fā)育進而影響細胞因子的分泌。自1994年Morrison首次報道維生素D受體基因多態(tài)性與骨密度的關系以來,對VDR基因多態(tài)性與糖尿病、結核等疾病、骨代謝、生長發(fā)育相關性的研究,一直是... 

【文章來源】：山東大學山東省 211工程院校 985工程院校 教育部直屬院校

【文章頁數(shù)】：60 頁

【學位級別】：碩士

【文章目錄】：
English Abstract
Chinese Abstract
List of Abbreviations
List of Tables
List of Figures
Chapter 1:General Introduction
    1.1 Asthma and its pathologic immune mechanisms
    1.2 Nuclear Vitamin D Receptor
    1.3 Regulation of the action of the VDR gene
    1.4 VDR and immunity
    1.5 Asthma and VDR polymorphisms
Chapter 2:Motivation,Hypothesis and Objectives
    2.1 Motivation
    2.2 Hypothesis
    2.3 Objectives
Chapter 3:Material and Methods
    3.1 Study Population
    3.2 Preparation of samples
        3.2.1 DNA Extraction
        3.2.2 DNA Quantification and Quality Analysis
    3.3 SNPs Selection
        3.3.1 Coding Polymorphisms
        3.3.2 Intronic Polymorphisms
    3.4 Genotyping
        3.4.1 Primer Design
        3.4.2 Polymerase Chain Reaction(PCR)
        3.4.3 Restriction fragment-length Polymorphisms Methood(RFLP)
    3.5 Statistical Analysis
        3.5.1 Genotypic and Allelic frequencies Calculus
        3.5.2 Hardy-Weinberg Equilibrium
        3.5.3 Genotypic and Allelic Association Analysis
        3.5.4 Linkage Disequilibrium and Haplotypes structure
        3.5.5 Sample size calculus
Chapter 4:Results
    4.1 SNPs Genotyping
    4.2 Hardy-Weinberg Equilibrium Assumption
    4.3 Association analysis between VDR Genetic Variants and Asthma
    4.4 The Strong association of ApaⅠ marker
    4.5 LD Measure and Haplotypes Analysis
Chapter 5:Discussion
    5.1 The selection of VDR gene as a candidate gene for this study
    5.2 The significant association found with VDR ApaⅠ polymorphism
    5.3 Principal other polymorphisms of VDR gene and their functionality
Chapter 6:Conclusion
    6 General conclusion
Referenees
Acknowledgement
Appendix
學位論文評閱及答辯情況表



本文編號：3580819