Osteoporosis is a major cause of morbidity among older Americans. The San Antonio Family Osteoporosis Study (SAFES) initiated in 1997 with the aim of identifying the determinants of bone mineral density (BMD) in large Mexican American families. A total of 897 subjects from 34 families were enrolled in the baseline phase of this study. Extensive genotypic information was made available on these subjects through their concurrent participation in a larger study, the San Antonio Family Heart Study (SAFHS), designed to identify the genetic determinants of atherosclerosis in these families. To date, we have obtained several exciting results from the SAFES. Foremost among these was the detection of very strong evidence for linkage of fore arm BMD to a region on chromosome 4p (multipoint led score = 4.3). We also observed associations of increased BMD with diabetes and of decreased BMD with carotid wall thickening, a subclinical measure of atherosclerosis in women aged 40 yr and older. This latter observation supports a growing body of evidence suggesting that osteoporosis and CVD share common etiologic determinants. We propose in the second 5-year funding period to re-measure BMD to assess 5-yr change in BMD and to begin fine mapp ng of the putative quantitative trait locus affecting BMD on chromosome 4p. Repeat DXA scans are currently being obtained in conjunction with the ongoing re-examination of SAFHS subjects. We will estimate hedtability of 5-yr changes in BMD and determine predictors of bone loss. We will utilize a positional candidate gene approach to pursue the major fine mapping aim. We will sequence coding and regulatory regions of 20 genes in the region of linkage to identify sequence variation and will then genotype all common variants in the full sample of SAFES participants for association and haplotype analysis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR043351-10
Application #
7211407
Study Section
Epidemiology of Clinical Disorders and Aging Study Section (ECDA)
Program Officer
Sharrock, William J
Project Start
1997-06-06
Project End
2009-01-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
10
Fiscal Year
2007
Total Cost
$427,425
Indirect Cost
Name
University of Maryland Baltimore
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
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Rampersaud, Evadnie; Mitchell, Braxton D; Naj, Adam C et al. (2008) Investigating parent of origin effects in studies of type 2 diabetes and obesity. Curr Diabetes Rev 4:329-39
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