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Free Content Epistatic Interactions between Genomic Regions Containing the COL1A1 Gene and Genes Regulating Osteoclast Differentiation may Influence Femoral Neck Bone Mineral Density

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Summary

Bone mineral density (BMD) is a primary risk indicator of osteoporotic fractures, which are largely determined by the actions of multiple genes. Genetic linkage studies have seldom explored epistatic interaction of genes for BMD. To evaluate potential genetic interactions for BMD at the femoral neck (FN) we conducted a variance component linkage analysis, to test epistatic effects between the genomic region containing the COL1A1 (collagen type I alpha 1) gene and the genomic regions containing genes regulating osteoclast differentiation (e.g. TNFRSF11A encoding RANK (receptor for activation of nuclear factor kappa B), TNFSF11 encoding RANKL (RANK ligand), IL1A (interleukin-1 alpha), IL6 (interleukin-6), etc) in 3998 Caucasian subjects from 434 pedigrees. We detected significant epistatic interactions between the regions containing COL1A1 with IL6 (p = 0.004) and TNFRSF1B encoding TNFR2 (tumor necrosis factor receptor 2) (p = 0.003), respectively. In summary, we identified the epistatic effects on BMD between regions containing several prominent candidate genes. Our results suggested that the IL6 and TNFRSF1B genes may regulate FN BMD variation through interactions with the COL1A1 gene, which should be substantiated by other, or population-based, association studies.
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Keywords: BMD; COL1A1; IL-6; TNFR2; epistasis; interaction; linkage; osteoclast

Document Type: Research Article

Affiliations: 1: Departments of Orthopedic Surgery and Basic Medical Science, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108 2: Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, NE 68131, USA

Publication date: March 1, 2007

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