Genetic association study between chitinase and atopic eczema phenotype in Chinese children.

Ching, Ka Wai.Thesis (M.Phil.)--Chinese University of Hong Kong, 2009.Includes bibliographical references (leaves [69-80]).Abstract also in Chinese.Abstract (in English) --- p.iiAbstract (in Chinese) --- p.vAcknowledgement --- p.viiiTable of Contents --- p.ixList of Tables --- p.xiiList of Figures --- p.xiiiGlossary of Terms and Abbreviations --- p.xvChapter Chapter 1: --- Introduction --- p.1Chapter 1.1 --- Introduction of Atopic Eczema (AE) --- p.1Chapter 1.1.1 --- Definition and classification of AE --- p.1Chapter 1.1.2 --- Epidemiology --- p.3Chapter 1.1.2.1 --- The hygiene hypothesis --- p.5Chapter 1.2 --- Pathogenesis and Etiology --- p.6Chapter 1.2.1 --- Biphasic type-1/type-2 T-helper lymphocyte (Thl/Th2) immunological responses --- p.6Chapter 1.2.2 --- Nature and involvements of immunoglobin E (IgE) --- p.8Chapter 1.2.3 --- Microbial colonization --- p.9Chapter 1.2.4 --- Cytokines involvement --- p.10Chapter 1.2.5 --- Pruritus inducing neurotrophic factors --- p.11Chapter 1.2.6 --- "Food allergens, aeroallergens" --- p.12Chapter 1.2.7 --- Dysregulation of innate immune system --- p.13Chapter 1.2.7.1 --- Dysregulation of antimicrobial peptides --- p.14Chapter 1.2.7.2 --- Skin barrier impairment --- p.14Chapter 1.2.8 --- Genetic predisposition --- p.15Chapter 1.3 --- Assessments of Atopic Eczema (AE) --- p.17Chapter 1.3.1 --- AE severity assessment --- p.17Chapter 1.3.1.1 --- Scoring of atopic dermatitis (SCORAD) system --- p.17Chapter 1.3.1.2 --- Nottingham eczema severity score (NESS) --- p.20Chapter 1.3.2 --- Dermatological parameter - skin hydration (SH) and transepidermal water loss (TEWL) --- p.22Chapter 1.4 --- Chitinase (CHIA) --- p.22Chapter 1.4.1 --- Chitin and CHIA --- p.22Chapter 1.4.2 --- Association of acid mammalian chitinase (AMCase) with asthma --- p.23Chapter 1.4.3 --- Hygiene hypothesis implies: AMCase and allergy relationship --- p.24Chapter Chapter 2: --- Hypothesis and Objectives --- p.25Chapter 2.1 --- Hypothesis - based on CHIA involvements in canine AE --- p.25Chapter 2.2 --- Hypothesis --- p.25Chapter 2.3 --- Objective 226}0ؤ based on AMCase single nucleotide polymorphism (SNPs) in asthma susceptibility --- p.25Chapter 2.4 --- Objectives --- p.27Chapter Chapter 3: --- Methodology --- p.28Chapter 3.1 --- Recruitment of cases and controls --- p.28Chapter 3.2 --- Assessment of clinical parameters --- p.29Chapter 3.2.1 --- Scoring of atopic dermatitis (SCORAD) system --- p.29Chapter 3.2.2 --- Nottingham eczema severity score (NESS) --- p.29Chapter 3.2.3 --- Dermatologic parameters --- p.29Chapter 3.2.3.1 --- Cutaneous bacterial colonization --- p.29Chapter 3.2.3.2 --- Skin hydration (SH) and transepidermal water loss (TEWL) --- p.30Chapter 3.3 --- Peripheral blood collection and genomic deoxyribonucleic acid (DNA) extraction --- p.30Chapter 3.4 --- Acid mammalian chitinase (AMCase) polymorphism genotyping --- p.31Chapter 3.4.1 --- Polymerase chain reactions (PCR) amplification of AMCase gene --- p.31Chapter 3.4.1.1 --- List of PCR reagents --- p.32Chapter 3.4.1.2 --- Electrophoresis reagents --- p.33Chapter 3.4.2 --- Restriction fragment length polymorphism (RFLP) analysis of AMCase and confirmation with direct sequencing --- p.33Chapter 3.5 --- Statistical analysis --- p.34Chapter Chapter 4: --- Results and Data Analysis --- p.36Chapter 4.1 --- Results --- p.36Chapter 4.1.1 --- Demographic data of cases and controls --- p.36Chapter 4.1.2 --- PCR amplification and RFLP analysis of AMCase gene --- p.37Chapter 4.1.3 --- PCR cycle sequencing of the PCR fragments --- p.40Chapter 4.2 --- Data analysis --- p.41Chapter 4.2.1 --- Data overview --- p.41Chapter 4.2.2 --- Genotypes distribution of AMCase polymorphisms --- p.43Chapter 4.2.2.1 --- Allele frequency comparison of AMCase single nucleotide polymorphism (SNPs) by chi-square --- p.43Chapter 4.2.2.2 --- Allele frequency comparison of AMCase SNPs by logistic regression analysis --- p.44Chapter 4.2.3 --- Haplotype frequency estimation via maximum likelihood algorithm --- p.45Chapter 4.2.4 --- Association of AMCase polymorphism with Atopic Eczema (AE) clinical parameters --- p.47Chapter 4.2.4.1 --- Peripheral blood eosinophil counts --- p.48Chapter 4.2.4.2 --- Serum immunoglobin E (IgE) level --- p.49Chapter 4.2.4.3 --- Dermatologic factors --- p.49Chapter 4.2.4.3.1 --- Cutaneous Staphylococcus aureus colonization --- p.49Chapter 4.2.4.3.2 --- Skin hydration (SH) and transepidermal water loss (TEWL) --- p.50Chapter Chapter 5: --- Discussion --- p.52Chapter 5.1 --- Data overview --- p.52Chapter 5.2 --- AMCase rs3806448 polymorphism was significantly different among AE cases and controls --- p.53Chapter 5.2.1 --- Allele frequency comparison of AMCase SNPs polymorphisms by chi-square --- p.53Chapter 5.2.2 --- Allele frequency comparison of AMCase SNPs polymorphisms by logistic regression analysis --- p.54Chapter 5.2.3 --- The possible genetic modification by rs3806448 homozygous recessive genotype --- p.55Chapter 5.3 --- "Significant difference of haplotype frequency, 2212 among case-control comparison" --- p.56Chapter 5.4 --- Strong associations between AMCase SNPs polymorphisms and clinical parameters of AE --- p.57Chapter 5.4.1 --- Peripheral blood eosinophil counts --- p.57Chapter 5.4.2 --- Dermatologic factors --- p.58Chapter 5.4.2.1 --- Cutaneous Staphylococcus aureus colonization --- p.58Chapter 5.4.2.2 --- Skin hydration (SH) and transepidermal water loss (TEWL) --- p.59Chapter 5.5 --- Limitation of the present study --- p.59Chapter Chapter 6: --- Conclusion and Future Prospect --- p.62Chapter 6.1 --- Conclusion --- p.62Chapter 6.2 --- Future prospect --- p.62Chapter Chapter 7: --- Appendices --- p.64Chapter Chapter 8: --- References --- p.6