COL1A1 Gene Detail

Type I collagen is the most abundant protein in the body and is a major structural component of bones, tendons, ligaments and joint cartilage. It accounts for 80% of proteins within bone tissue and is the main extracellular matrix protein that is calcified within bone, making it responsible for bone strength and toughness. A loss of collagen observed with age leads to a decline in bone strength and an increased risk of fractures

COL1A1 Sp1 is a G>T single-nucleotide polymorphism (SNP) on human chromosome 17 known to modulate expression of the alpha 1 chain of collagen type 1. This functional variant has adverse effects on bone composition and mechanical strength and associations between the COL1A1 Sp1 SNP, bone mass, fracture risk and osteoporosis has been observed in several populations and meta-analyses.

The COL1A1 Sp1 T allele leads to an increased binding affinity for the Sp1 transcription factor and greater transcription of COL1A1. This variant results in an increased ratio of collagen type I α1 protein relative to α2. These unbalanced collagen fibres pose a risk factor for osteoporosis and bone fragility by influencing bone mass and quality.

Figure 1 to the right taken from Lin et al (2009) illustrates ‘Suggested mechanism of osteoporosis associated with polymorphisms in the 5′ flank of COL1A1’ (Lin et al). Polymorphisms in the 5′ flank of COL1A1 regulate binding affinity of several critical nuclear binding proteins including Nmp4, Osterix and Sp1. This increases transcription of haplotype 2 which causes increased expression of COL1A1 mRNA, and over production of the alpha 1 chain relative to alpha 2, such that a proportion of collagen produced by osteoblasts is in the form of alpha 1 homotrimers. This adversely affects mineralization of bone, resulting in reduced BMD and an increased risk of fracture. (Human Molecular Genetics, Volume 18, Issue 15, 1 August 2009, Pages 2729–2738, https://doi.org/10.1093/hmg/ddp205).

Rojano-Mejía et al. 2013 showed that individuals with the COL1A1 Sp1 G allele tend to have a greater bone mineral density (BMD) at the lumbar spine. Singh et al. 2013 similarly observed a dose effect of the COL1A1 Sp1 T allele on lumber spine BMD, with individuals with the T allele presenting with a lower BMD and higher risk of osteoporosis. The association of the COL1A1 gene with low BMD, osteoporosis and subsequent fracture risk has been observed in Caucasian, Indian, Mexican, Kazakh and Chinese female populations. Marini et al. 2013 similarly observed an association between theCOL1A1 Sp1 TT genotype and low BMD at both spine and femur sites in an Italian mixed male and female population.

Osteoporosis is a multifactorial disease influenced by both genetic and environmental factors that need to be considered. Screening of genetic variations associated with risk for osteoporosis may enable the early detection of at-risk individuals, allowing the optimization of preventative interventions as well as treatment.

The production of type I collagen plays an important role in the differentiation of osteoblasts, maintaining BMD, bone mineral content and increasing the amount of type I collagen in the bone matrix. Supplementation of hydrolysed collagen has been found to increase growth and differentiation of osteoblasts cells and reduce osteoclasts, improving bone composition and strength. This affect occurs through the regulation of COL1A1, involved in collagen synthesis. In mice, treatment with bovine collagen peptides was found to increase the proliferation of osteoblast cells, and positively influenced osteoblast differentiation and mineralized bone matrix formation.

A 2014 randomized control trial investigated the effect of a calcium-collagen chelate supplement on bone loss in postmenopausal women with osteopenia. Daily supplementation of 5g of hydrolysed collagen calcium chelate in combination with 500 mg of elemental calcium and 200 IU of vitamin D led to a substantially lower loss of BMD after 1 year in comparison to patients receiving only 500 mg of elemental calcium and 200 IU of vitamin D. This study supports the use of hydrolysed collagen calcium chelate in preventing osteoporosis in at risk patients.