Mexican-American Family Osteo Study (MXFOS)
Dr. Braxton Mitchell, P.I.
Osteoporosis is a major cause of morbidity among older Americans. The San Antonio Family Osteoporosis Study (SAFOS) 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 SAFOS. Foremost among these was the detection of very strong evidence for linkage of forearm BMD to a region on chromosome 4p (multipoint lod 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 mapping 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 heritability 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 SAFOS participants for association and haplotype analysis.
(as of 22 November 2010)
Shaffer JR, Kammerer CM, Dressen AS, Bruder JM, Bauer RL, Mitchell BD. Rate of bone loss is greater in young Mexican American men than women: The San Antonio Family Osteoporosis Study. Bone 47:49-54, 2010. PMCID: PMC2891113 [Available on 2011/7/1]
Hoppman N, McLenithan JC, McBride DJ, Shen H, Bruder J, Bauer RL, O’Connell JR, Streeten EA, Shuldiner AR, Kammerer CM, Mitchell BD. Common variants in fibroblast growth factor binding protein 1 (FGFBP1) are associated with bone mineral density and influence gene expression in vitro. Bone 47(2):272-280, 2010. PMCID: PMC2902654 [Available on 2011/8/1]
Mitchell, BD, Bauer, RL, Beck, TJ, Bruder, J, Kemmerer, CM, McBride, DJ, O'Connell, JR. Genetics of Bone Mineral Density and Bone Loss in Mexican Americans. (Abstract).
Shaffer JR, Kammerer CM, Bruder JM, Cole SA, Dyer TD, Almasy L, MacCluer JW, Blangero J, Bauer RL, Mitchell BD. Quantitative Trait Locus on Chromosome 1q Influences Bone Loss in Young Mexican American Adults. Calcif Tissue Int 84:75–84, 2009. PMCID: PMC2680710
Shaffer JR, Kammerer CM, Bruder JM, Cole SA, Dyer TD, Almasy L, MacCluer JW, Blangero J, Bauer RL, Mitchell BD. Genetic influences on bone loss in the San Antonio Family Osteoporosis study. Osteoporos Int. 2008 Dec;19(12):1759-67. PMCID: PMC2712667.
Ioannidis JPA, Mandy Y. Ng MY, Sham PV, Zintzaras E, Lewis C, Deng H-W, Econs MJ, Karasik D, Devoto M, Kammerer CM, Spector T, Andrew T, Cupples LA, Foroud T, Kiel DP, Koller D, Langdahl B, Mitchell BD, Peacock M, Recker R, Shen H, Sol-Church K, Spotila LD, Uitterlinden AG, Wilson SG, Kung AWC, Ralston SH. Meta-analysis of genome wide scans provides evidence for gender and site specific regulation of bone mass. J Bone Miner Res 22:173-183, 2007.
Shaffer JR, Kammerer CM, Rainwater DL, O’Leary DH, Bruder JM, Bauer RL, Mitchell BD. Decreased bone mineral density is correlated with increased subclinical atherosclerosis in older, but not younger, Mexican American women and men: The San Antonio Family Osteoporosis Study. Calcif Tiss Internat 81:430-441, 2007.
Kammerer CM, Dualan AA, Samollow PB, Périssé ARS, Bauer RL, MacCluer JW, O’Leary DH, Mitchell BD. Bone mineral density, carotid artery intimal medial thickness, and the Vitamin D Receptor BsmI polymorphism in Mexican American women. Calcified Tissue Internat 75:292-298, 2004.
Kammerer CK, Schneider JL, Cole SA, HixsonJE, Samollow PB, O’Connell JR, Perez R, Dyer TD, Almasy L, Blangero J, Bauer RL, Mitchell BD. Quantitative trait loci on chromosomes 2p, 4p and 13q influence bone mineral density of the forearm and hip in Mexican Americans. J Bone Min Res 18:2245-2252, 2003.
Kao WHL, Kammerer CM, Schneider JL, Bauer RL, Mitchell BD. Type 2 diabetes is associated with increased bone mineral density in Mexican American women. Arch Med Res 34:399-406, 2003.
Mitchell BD, Kammerer CM, Schneider JL, Perez R, Bauer RL. Genetic and environmental determinants of bone mineral density in Mexican Americans: Results from the San Antonio Family Osteoporosis Study. Bone 33:839-846, 2003.