Gene expression and methylation of matrix metalloproteinase-13 and osteoarthritis & Burden of risk alleles for complex traits in the Newfoundland and Labrador population

• Main Author: Harper, Patricia Emily Rose
• Format: Thesis
• Language: English
• Published: Memorial University of Newfoundland 2015
• Subjects: Newfoundland
• Online Access: https://research.library.mun.ca/11594/; https://research.library.mun.ca/11594/1/thesis.pdf

PART I To evaluate the role of MMP-13, a catabolic enzyme, in osteoarthritis (OA) pathogenesis, we utilized a case-control study design to analyze cartilage samples obtained from 48 OA patients and 30 healthy controls. We found that MMP-13 expression was significantly increased in OA-affected cartilage compared to healthy cartilage. A CpG site in the promoter of MMP-13 was also significantly demethylated in osteoarthritic cartilage but was not correlated with the gene expression. The results suggest a potential role for MMP-13 in OA pathogenesis. PART II Founder populations, such as Newfoundland & Labrador (NL), often have higher prevalences of genetic disease, making them ideal for disease gene mapping. Mean frequencies of common disease-associated alleles from over 140 diseases were evaluated in the NL population. The mean risk allele frequencies of coronary heart disease, celiac disease and bladder cancer were elevated in NL when compared to an out-bred population. The elevated disease allele frequencies were in concert with the high prevalence of the diseases in NL. This novel approach to studying disease risk in a population may provide new insights into genetic risk of complex conditions and could be used to inform health policy.