published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Nursing Studies / Master / Master of Nursing in Advanced Practice

published_or_final_version / Public Health / Master / Master of Public Health

published_or_final_version / Sports Science / Master / Master of Science in Sports Science

published_or_final_version / Community Medicine / Master / Master of Public Health

published_or_final_version / Behavioral Health / Master / Master of Social Sciences

Background and objectives: Recent genome-wide association (GWA) studies conducted in Caucasian populations have significantly expanded the list of confirmed and potential susceptibility genes for obesity and type 2 diabetes. The major objective of this thesis was to establish the role of the previously identified obesity- and T2DM-susceptibility genes in the Hong Kong Southern Chinese population. Major findings: In a cross-sectional case-control study of Southern Chinese which involved 470 obese cases and 700 normal-weight controls, significant associations with obesity were demonstrated in 7 of 13 single nucleotide polymorphisms (SNPs) that have shown significant associations with obesity and/or body mass index (BMI) in previous Caucasian GWA studies. These SNPs are located within or near the GNPDA2, FTO, MC4R, KCTD15, SFRS10-ETV5-DGKG, SEC16B-RASAL2 and NEGR1 loci. The combined genetic risk score (GRS) of the 13 studied SNPs was associated with an increased risk for obesity. The GNPDA2 rs10938397, FTO rs8050136, and MC4R rs17782313, which showed the most significant associations with obesity, were further examined for their associations with persistent central obesity and the metabolic syndrome (MetS). Both rs8050136 and rs10938397 were significantly associated with persistent central obesity. rs10938397 was also associated with the MetS. The combined GRS of these 3 SNPs showed significant associations with both persistent central obesity and persistent MetS. Nineteen multimarker-tagging SNPs that span a well-defined LD block of the FTO gene were evaluated for their associations with obesity in a case-control study which involved 249 cases and 400 controls. rs16952522 was found to be significantly associated with obesity, in addition to the well-known SNP rs8050136. These 2 SNPs were nominally associated with T2DM, although the associations were abolished after adjustment for age, sex and BMI. However, the GA haplotype composed of the risk alleles of these 2 SNPs was significantly associated with T2DM, independent of BMI. Seventeen previously identified T2DM-associated SNPs were investigated for the associations with glycaemic progression in an 8-year follow-up study which involved 518 cases and 998 controls. Their combined GRS was associated with an increased risk for glycaemic progression. A significant association with glycaemic progression was found with CDKN2A/B rs10811661. Moreover, KCNJ11 rs5219 and IGF2BP2 rs11711477 also showed potential associations with glycaemic progression. In the subsequent 12-year follow-up study, which involved 200 cases and 903 controls, the CDKN2A/B rs10811661 showed a significant independent association with incident T2DM. The KCNJ11 E23K (rs5219) variant was examined for its association with diabetes development in a 12-year prospective study. It was found to be significantly associated with the development of prediabetes but not with the development of T2DM. However, in a meta-analysis which involved 15680 subjects across different populations, this variant could indeed predict T2DM. Conclusions: The findings of this thesis have provided novel evidence supporting the role of the GWA studies-identified obesity- and T2DM-associated genetic variants as genetic markers of obesity and T2DM among Southern Chinese in Hong Kong, and suggest that the GNPDA2, FTO and MC4R genes confer susceptibility to obesity and that the CDKN2A/B and KCNJ11 genes may play a role in diabetes development. / published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Zoology / Master / Master of Philosophy

(Uncorrected OCR) Abstract Many studies have been conducted in Caucasian populations on the optimal body mass index cut-off for obesity, as well as the relationship between body mass index and percentage body fat and their associations with cardiovascular risk factors. However, few studies of this kind have been conducted in the Hong Kong Chinese population, This research is deemed to be important due to ethnic differences between Asians and Caucasians, Therefore, this dissertation aims to determine any ethnic differences from a sample of the local Hong Kong Chinese population, in order to advance health care policies controlling known cardiovascular risk factors. A total of 800 subjects were randomly selected from a pool of subjects participated in a Hong Kong Cardiovascular Risk Factor Prevalence study conducted in 1994-1996. These subjects were contacted and 453 disease-free subjects (210 males and 243 females) consented to participate in the current study, Data collected included serum and blood pressure measurements, body mass index, percentage body fat measured by bioelectrical impedance analysis, and a self-completed cardiovascular risk factor questionnaire, The mean age of the 453 subjects was 51.64 years (SD=12.3). When obesity was defined as percentage body fat ~ 25 and 2: 30 in males and females respectively, 23 kg/m2 was found to be the optimum cut-off value, with 78% correct classification (95% CI = 69%-87%). The corresponding sensitivity and specificity were 88% (95% CI = 81 %-95%) and 67% (95% CI = 57%-77%) respectively. On the other hand, if obesity was defined as percentage body fat ~ 25 and 2: 35 in males and females respectively, then 25 kg/m2 was found to be the best cut-off value with 82% correct classification (95% CI = 74%-90%). The corresponding sensitivity and specificity were 78% (95% CI = 69%-87%) and 85% (95% Cl = 78%-92%) respectively. Moreover, body mass index was found to be quadratically body fat. The quadratic relationship did not appear two genders, except that the percentage body fat of of females by 9.97 (SE=0.33). Finally, except for total cholesterol, high density lipoprotein cholesterol, and fasting glucose, body mass index did not provide any substantial information additional to percentage body fat on serum and blood pressure measurements. was the only measure on which percentage body fat did additional to body mass index. When waist-hip body mass index and percentage body fat,. except for body mass index did not have additional information on measurements when percentage body fat or/and [n conclusion, the optimal body mass index cut-off for obesity in Hong Kong Chinese was lower than the 30kg/m2 recommended by the World Health Organization, a clear reflection of ethnic difference between Asians and Caucasians. The quadratic relationship between percentage body fat and body mass index was similar in Hong Kong Chinese as in Caucasians and Blacks. Moreover, percentage body fat together with waist-hip-ratio were found to be better indicators of cardiovascular risk factors in Hong Kong. This was the first time such findings were found in the Hong Kong Chinese population. II / abstract / toc / Medical Sciences / Master / Master of Medical Sciences