Approved research

Elevated plasma levels of Cthrc1 in subjects with red hair: What are the consequences for bone, liver, vascular disease, diabetes and muscle?

Lay summary

We discovered that Cthrc1 is novel hormone made by the pituitary gland (Stohn et al. PlosOne 2012). Studies in mice showed that absence of Cthrc1 causes fatty liver formation, reduced grip strength and reduced bone density. Having established a sensitive assay, we found that Cthrc1 plasma levels in healthy subjects are very low with the exception of subjects with red hair (melanocortin receptor-1 variants) who had up to several hundred fold higher levels. Therefore, we are very interested how hair color and melanocortin receptor-1 genotype (when available) correlates with grip strength, bone density, vascular disease, diabetes and steatosis. The frequency of mutant melanocortin receptor-1 alleles in northern european countries such as the UK are estimated to be 50%. It is established that subjects with red hair and associated non-tanning skin are more likely to develop skin cancer, yet the mutant allele does not appear to be under selective pressure in these countries. If we find positive correlations between red hair (and assumed elevated Cthrc1 blood levels) and increased bone density, grip strength and resistance to fatty liver formation, future therapies can be developed to treat osteoporosis, muscle weakness and liver disease. The database will be mined for correlations between red hair, non- or poorly tanning skin versus darker, easily tanning skin with respect to osteoporosis, bone mineral density (heel BMD), bone fractures, hand grip strength, atherosclerosis, vascular disease, alcoholic liver disease and fatty liver. In addition, we would be very interested in obtaining information on the melanocortin receptor-1 genotype when it becomes available (July 2015?). The latter will predict to what degree signaling via the melanocortin receptor-1 is inhibited. We would like to include the full cohort for analysis.