To identify subjects with diabetes who may be at risk of developing osteoporosis and fractures, we analysed bone mineral density in relation to the biochemical markers of bone turnover, calcium homeostasis and the COL1A1 genotype in a group of premenopausal women with Type I (insulin-dependent) diabetes mellitus (n = 31), Type II (non-insulin dependent) diabetes mellitus (n = 21) and control subjects (n = 20).
We conclude that the COL1A1 Sp1 polymorphism is a functional genetic variant that predisposes to osteoporosis by complex mechanisms involving changes in bone mass and bone quality.
After adjusting for all other variables, the osteoporosis densitometric criteria variable was the most strongly associated with fracture (OR = 5 [1.8-13.3]) followed by COLIA1 (OR = 2.1 [1-4.3] per copy of the 'T' allele).
Most work in this area of osteoporosis research has focused on the candidate gene approach, which has identified several candidate genes for osteoporosis, including genes encoding the vitamin D receptor (VDR), oestrogen receptors (alpha and beta), apolipoprotein E, collagen type I alpha 1 and methylenetetrahydrofolate reductase, amongst many others.
Some cases of otosclerosis and osteoporosis could share a functionally significant polymorphism in the Sp1 transcription factor binding site in the first intron of the COL1A1 gene.
This study demonstrates for the first time that pyrosequencing can be used for rapid identification of the osteoporosis-associated single nucleotide polymorphism (SNP) in the COL1A1 gene.
Some cases of otosclerosis and osteoporosis could share a functionally significant polymorphism in the Sp1 transcription factor binding site in the first intron of the COL1A1 gene.
Type I collagen is the most abundant protein of bone matrix, and the collagen type I alpha 1(COLIA1) gene has been considered one of the most important candidate genes for osteoporosis.
The results obtained until now can be divided into three sections: (1) genetic analysis of bone mass/size/geometry characteristics (OP) and traits related to hand OA; (2) pedigree-based investigation of circulating levels of calciotropic hormones, growth factors, cytokines, and biochemical indices of bone and cartilage remodelling; (3) linkage and linkage disequilibrium study of several candidate genes, such as estrogen receptor alpha, collagen type I alpha 1, genes related to extracellular inorganic pyrophosphate transport and OP/OA phenotypes, including biochemical variables.
This is consistent with a model whereby increased COL1A1 transcription predisposes to osteoporosis, probably by increasing production of the alpha 1 chain and disrupting the normal ratio of collagen type 1 alpha 1 and alpha 2 chains.
Polymorphisms in the 5' flank of COL1A1 gene have been implicated as genetic markers for susceptibility to osteoporosis, but previous studies have yielded conflicting results.
Collagen type I alpha 1 (COL1a1), which encodes the primary subunit of type I collagen, the main structural and most abundant protein in vertebrates, harbors hundreds of mutations linked to human diseases like osteoporosis and osteogenesis imperfecta.
A G→T polymorphism in the regulatory region of the collagen type I alpha 1 (COLIAI) gene at a recognition site for transcription factor Sp1 has been strongly associated with osteoporosis.
In comparison to age-matched controls we detected profound changes in the transcriptome in hMSC-OP, e.g. enhanced mRNA expression of known osteoporosis-associated genes (LRP5, RUNX2, COL1A1) and of genes involved in osteoclastogenesis (CSF1, PTH1R), but most notably of genes coding for inhibitors of WNT and BMP signaling, such as Sclerostin and MAB21L2.
Little of the underlying disease etiology has been elucidated thus far, although several studies have suggested that COL1A1 may play a role based on its importance in bone metabolism and other diseases like osteoporosis and osteogenesis imperfecta.