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Title: The biochemical and genetic basis of ethnic differences in osteoporotic fracture incidence
Author: Beavan, S. R.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1998
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The aim of this thesis was a preliminary investigation of nutritional and biochemical factors which may be implicated in ethnic differences in fracture risk. Investigation of polymorphic loci of the vitamin D receptor gene revealed that the frequency of B and t alleles was considerably greater in the British subjects than in their Gambian or Chinese counterparts (p<0.001). The frequency of the "s" allele of the polymorphic SP1 binding site in the collagen 1α1 gene was also considerably greater in the British subjects than in the Gambian (p<0.02) or Chinese (p<0.001) subjects. The vitamin K status of bone, indicated by the γ-carboxylation of plasma osteocalcin, was determined in eleven premenopausal women of each group and in postmenopausal Gambian (n=50), British (n=31) and Chinese (n=23) subjects. In all groups, undercarboxylation was significantly higher post- than premenopause, but this was related to the higher total osteocalcin concentration present postmenopause. After consideration of differences in total osteocalcin, undercarboxylation was highest in the British, intermediate in the Gambian and lowest in the Chinese subjects irrespective of menopausal status. Possible determinants of osteocalcin γ-carboxylation were investigated. There was a direct relationship between plasma vitamin K concentration and osteocalcin γ-carboxylation in the British subjects, and a direct relationship between plasma triglyceride concentration and osteocalcin carboxylation in the Gambian and Chinese subjects. Apolipoprotein E2 allele was associated with increased γ-carboxylation in the British and Chinese subjects, but there was little indication of a an influence of plasma vitamin D concentration. Differences in plasma vitamin K concentration were observed between the ethnic groups, being significantly higher in the postmenopausal Chinese compared with the British (117% p≤0.0001) and Gambian subjects (103% p≤0.0001). These data suggest genetic differences may exist in calcium homeostasis and the collagen structure of bone, along with differences in vitamin K status and the γ-carboxylation system of osteoblasts, which may be implicated in ethnic variation in osteoporotic fracture risk.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available