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Epistatic Interactions between Genomic Regions Containing the COL1A1 Gene and Genes Regulating Osteoclast Differentiation may Influence Femoral Neck Bone Mineral Density
Author(s) -
Yang TieLin,
Shen Hui,
Xiong DongHai,
Xiao Peng,
Guo Yan,
Guo Yanfang,
Liu YaoZhong,
Recker Robert R.,
Deng HongWen
Publication year - 2007
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/j.1469-1809.2006.00313.x
Subject(s) - epistasis , rankl , osteoclast , rank ligand , genetics , biology , gene , pedigree chart , candidate gene , bone mineral , genetic linkage , population , osteoporosis , receptor , endocrinology , medicine , environmental health , activator (genetics)
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.