Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 163-189).

Thesis (Ph. D.)--University of Missouri-Columbia, 2001. / Typescript. Vita. Includes bibliographical references. Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 2001. / Typescript. Vita. Includes bibliographical references. Also available on the Internet.

Thesis (M.S.)--University of Missouri-Columbia, 2003. / RGL after WOC in title is in superscript. Typescript. Includes bibliographical references. Also available on the Internet.

Thesis (M.S.)--University of Missouri-Columbia, 2003. / RGL after WOC in title is in superscript. Typescript. Includes bibliographical references. Also available on the Internet.

Thesis (M. Phil.)--University of Hong Kong, 1987.

This thesis presents genetic studies of atopic dermatitis (AD) and IgA deficiency in dogs. AD is a chronic inflammatory and pruritic skin disorder caused by allergic reactions against environmental allergens. Both genetic and environmental factors are involved in the development of Canine AD (CAD) and human AD. In Paper I, we performed genome-wide association studies (GWAS) and identified a locus on chromosome 27 significantly associated with CAD in German shepherd dogs (GSDs). The locus contains several genes and fine-mapping indicated strongest association close to the candidate gene PKP2. In Paper II, we performed additional fine-mapping and identified four highly associated SNPs located in regions with transcriptional regulatory potential in epithelial and immune cells. The risk alleles were associated with increased transcriptional activity and the effect on expression was cell-type dependent. These data indicate that multiple cell-type specific enhancers regulate the expression of PKP2, and/or the neighboring genes YARS2, DNM1L and FGD4, and predispose GSDs to CAD. IgA deficiency is the most common primary immune deficiency disorder in both humans and dogs, characterized by a higher risk of recurrent mucosal tract infections, allergic and other immune-mediated diseases. In Paper III, we performed the widest screening (to date) of serum IgA levels in dog breeds (Ndogs=1267, Nbreeds=22) and defined eight breeds as predisposed to low IgA levels. In Paper IV, we performed GWAS in four of the breeds defined as prone to low IgA levels. We used a novel percentile groups-approach to establish breed-specific cut-offs to perform analyses in a close to continuous manner. In total, 35 genomic loci were suggestively associated (p<0.0005) to IgA levels, and three genomic regions (including the genes KIRREL3 and SERPINA9) were genome-wide significantly associated with IgA levels in GSDs. A ~20kb long haplotype on chromosome 28, significantly associated to IgA levels in Shar-Pei dogs, was positioned within the first intron of the gene SLIT1 overlapping with a possible dog domestication sweep. This thesis suggests novel candidate genes involved in two immune-mediated disorders in the dog. Hopefully, these results will become an important resource for the genetic research of the corresponding human diseases.

Despite the medical advances in recent decades, cardiovascular disease (CVD) remains one of the leading causes of mortality in most developing countries. Ongoing efforts have been focused on evaluating new strategies targeting on novel risk factors. Vitamin D deficiency, a previously neglected condition, has recently attracted much attention from the scientific community with its potential extra-skeletal effects. There is accumulating evidence from epidemiological studies that a suboptimal 25-hydroxyvitamin D [25(OH)D] level is associated with all-cause and cardiovascular mortality, increased risk of coronary heart disease, stroke and peripheral vascular disease, and various traditional CVD risk factors including hypertension, diabetes mellitus (DM) and metabolic syndrome. Several theories have been proposed to explain these relationships but none receive universal recognition. There is recent laboratory evidence that vitamin D may exert specific effects in patients with DM. However, relationships between vitamin D deficiency and supplementation on vascular function in this group of patients are unclear. In this dissertation, I sought to explore the effects of vitamin D deficiency on vascular function in patients with type II DM in a cross-sectional study. In the later part, the results of a randomized controlled trial investigating the effects of daily vitamin D supplementation in type II DM patients are presented and discussed. The cross-sectional study (Chapter 3) investigated the association of vitamin D status with endothelial function as measured by brachial flow-mediated dilation (FMD) and circulating endothelial progenitor cell (EPC) numbers in 280 patients with type II DM. The results showed that suboptimal vitamin D status was more common among patients with DM. Furthermore, patients with vitamin D deficiency had significantly lower brachial FMD (mean difference = -1.43%, 95% CI: -2.31 to -0.55, P = 0.001) and CD133/KDR+ EPC counts (mean difference = -0.12%, 95% CI: -0.21 to -0.02, P = 0.022) than those with sufficient vitamin D after adjustment for age, sex and cardiovascular risk factors, including HbA1c levels. Based on these positive results, the objectives of the randomized controlled trial (Chapter 4) were to study and confirm the effects of daily oral vitamin D supplementation on the vascular function in this group of patients. Over a 12-week period, 100 DM patients with suboptimal vitamin D status were randomized to receive 5,000 IU/day vitamin D or placebo. There were no reported adverse events including hypercalcemia, although a slight increase in serum ionized calcium (treatment effect 0.037 mmol/L, P = 0.018) was recorded in the vitamin D group. Despite a significant improvement in serum 25(OH)D in the treatment group, supplementation of vitamin D did not result in any significant improvement in vascular function as determined by FMD, circulating EPC count or arterial stiffness (all P > 0.05). Furthermore, the serum level of high-sensitivity C-reactive protein, oxidative stress markers, low- and high-density lipoprotein and glycated haemoglobin were also similar between two groups (all P > 0.05). The results of this study did not support a therapeutic role of supplementation with vitamin D for cardiovascular benefits. In conclusion, the results of these studies demonstrated that deficiency of vitamin D was associated with worse vascular function in patients with type II DM. However, vitamin D supplementation did not result in any significant benefits on vascular function or improvement in traditional CVD risk factors in DM patients. Further large clinical trials on vitamin D supplementation in patients with DM using clinical outcomes rather than surrogate CVD markers are necessary to confirm its benefits. / published_or_final_version / Medicine / Master / Master of Research in Medicine

Background Vitamin D deficiency is prevalent in many places across the world. Breastfeeding has been suggested to be a significant predictor of vitamin D deficiency during infancy, which is preventable through proper supplementation. However, whether Hong Kong should adopt the international recommendation for supplementation of exclusive breastfed infants is still not yet answered. Objective: To review the available evidence regarding the association between breastfeeding and vitamin D deficiency during infancy, as well as the effectiveness of vitamin D supplementation of breastfed infants as an intervention measure. Methods A total of 5112 potentially relevant articles were searched and identified from MEDLINE (OVID, Pubmed), Science Citation Index Expanded (ISI Web of Science), Cochrane Central Register of Controlled Trials, EMBASE, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Chinese database (CNKI) without restriction from inception to July-06-2012. 5065 articles were excluded after the initial scanning of title and abstracts. 36 were subsequently excluded due to methodological issues. A total of 11 studies were included and reviewed by two independent reviewers. Results This review pooled together a total of 1126 exclusively breast-fed infants for less than one year old from 11 studies. The pooled average prevalence of vitamin D deficiency was 54.2%. The association between breastfeeding and vitamin D deficiency during infancy has been reported consistently, and it was found to be one of the strongest predictors of vitamin D deficiency for infants less than one year old. Sunlight exposure, season, and skin pigmentation were also found to be important affecting factors. Supplementation to breastfed infants with the dosages as recommended by American Academy of Pediatrics (AAP) seem to be effective in lifting up the vitamin D levels. Conclusions The Hong Kong Government and relevant health sectors should conduct local epidemiological study to investigate the problem of concern among our breast-fed infants, and seriously consider or evaluate the AAP recommendation of supplementation. / published_or_final_version / Public Health / Master / Master of Public Health

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences