Faculty Collaboration Database

Epistatic interactions between genomic regions containing the COL1A1 gene and genes regulating osteoclast differentiation may influence femoral neck bone mineral density. Ann Hum Genet 2007 Mar;71(Pt 2):152-9

Date

03/03/2007

Pubmed ID

17331078

DOI

10.1111/j.1469-1809.2006.00313.x

Scopus ID

2-s2.0-34047275241 (requires institutional sign-in at Scopus site)   4 Citations

Abstract

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.

Author List

Yang TL, Shen H, Xiong DH, Xiao P, Guo Y, Guo YF, Liu YZ, Recker RR, Deng HW

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Bone Density
Cell Differentiation
Collagen Type I
Epistasis, Genetic
Female
Femur Neck
Genetic Linkage
Genotype
Humans
Interleukin-6
Male
Middle Aged
Models, Genetic
Osteoclasts
Receptors, Tumor Necrosis Factor
Receptors, Tumor Necrosis Factor, Type II