Hip Bone Mineral Density and Vitamin D Levels Are Increased in Healthy Male Carriers of Arg82Cys in CD300LG and Points to CD300LG As a Novel Gene in Bone and Vitamin D Metabolism

Presentation Number: OR13-3
Date of Presentation: June 21st, 2014

Julie Støy*1, Ulla Kampmann1, Lars Rejnmark2, Jørgen Rungby3, Ivan Brandslund4, Cramer Christensen4, Torben Hansen5, Oluf Pedersen5 and Niels Møller1
1Aarhus University Hospital, Aarhus C, Denmark, 2Aarhus University Hospital, Aarhus C, 3Rigshospitalet, Copenhagen, Denmark, 4Vejle Hospital, Vejle, Denmark, 5University of Copenhagen, Copenhagen, Denmark


The genetics of osteoporosis have been scrutinized in large-scale genome-wide association studies (GWAS) with a large number of common genetic variants identified, each of which exerts subtle effects on disease susceptibility. In a recent whole exome sequencing project of 2000 Danish individuals, a rare amino acid polymorphism in CD300LG was found to associate with low fasting HDL-cholesterol levels and high triglyceride levels. The rs72836561 CT polymorphism in CD300LG has not been detected in GWAS of osteoporosis, most likely due to its relatively low frequency, but a negative correlation between BMD and HDL-cholesterol has been suggested. Mice studies have shown changes in bone structure and quality in CD300LG knockout mice. We therefore performed a bone-related phenotype characterization of human carriers of the CD300LG risk-allele including an evaluation of BMD and a biochemical profile relevant to bone metabolism.

Methods: 20 healthy males with the CD300LG rs72836561 CT genotype were matched on age and BMI with 20 healthy males with the CC genotype. The 40 study subjects were examined by DEXA scan of the hip, lumbar spine, distal forearm, and whole body. The biochemical profile included markers of bone formation, bone reabsorption, vitamin D turn-over, and calcium homeostasis.  

Results: CT-carriers had a tendency to higher whole body BMD (1.19 g/cm2 (95 % confidence interval (CI), 1.15-1.24) versus 1.16 (1.11-1.20); p=0.24) and a higher BMD in the hip (0.99 g/cm2 (95 % CI, 0.93-1.05) versus 0.95 (0.91-0.99); p=0.21) compared to the CC-carriers. The differences in BMD were statistically significant or borderline significant after adjustment for vitamin D level (p=0.064 and p=0.045, respectively). The same trend was observed for BMD in the lumbar spine and in the forearm (adjusted p-values of 0.22 and 0.06, respectively). Vitamin D levels were higher in the CT-carriers 59.4 nmol/l (95 % CI, 51.7-67.1) compared to the CC-carriers (47.5 nmol/l (39.0-56.1)); p=0.037. Exclusion of two study subjects with daily intake of a vitamin D and calcium supplement, preserved a significant difference in BMD of the hip (p=0.023). A trend towards a higher level of the bone formation markers, osteocalcin and bone-specific alkaline phosphatase, among CC-carriers was observed (p=0.09 and p=0.07, respectively).  

Conclusion: The CD300LG rs72836561 CT-genotype may affect vitamin D and bone metabolism in healthy male carriers in terms of higher levels of Vitamin D and higher hip BMD. This points to CD300LG as a potential novel gene in the regulation of bone and vitamin D metabolism. The underlying mechanisms are currently unknown and future studies are warranted to test the possible association in a larger study cohort.


Nothing to Disclose: JS, UK, LR, JR, IB, CC, TH, OP, NM