Promoter polymorphisms in the chitinase 3-like 1 gene influence the serum concentration of YKL-40 in Danish patients with rheumatoid arthritis and in healthy subjects
1 Department of Clinical Immunology, Aalborg Hospital, Aarhus University Hospital, Reberbansgade, Pobox 561, 9000, Aalborg, Denmark
2 Department of Haematology, Aalborg Hospital Science and Innovation Center, Aarhus University Hospital, Soenderskovvej 15, 9000, Aalborg, Denmark
3 Department of Cardiology, Center for Cardiovascular Research, Aalborg Hospital, Aarhus University Hospital, Soenderskovvej 15, 9000, Aalborg, Denmark
4 Department of Rheumatology, Copenhagen University Hospital, Hvidovre and Glostrup, Ndr, Ringvej 57, 2600, Glostrup, Denmark
5 Department of Medicine, Copenhagen University Hospital, Herlev - Ringvej 75, 2730 Herlev, Denmark
6 Department of Oncology, Copenhagen University Hospital, Herlev - Ringvej 75, 2730 Herlev, Denmark
Arthritis Research & Therapy 2011, 13:R109 doi:10.1186/ar3391Published: 29 June 2011
The present study investigates the association between single nucleotide polymorphisms (SNPs) in the chitinase 3-like 1 (CHI3L1) gene and serum concentrations of YKL-40 in Danish patients with rheumatoid arthritis (RA) and healthy controls as well as the association with RA in the Danish population. The CHI3L1 gene is located on chromosome 1q32.1 and encodes the YKL-40 glycoprotein. YKL-40 concentrations are elevated in the serum of patients with RA compared to healthy subjects, and YKL-40 has been suggested to be an auto-antigen and may play a role in development of RA and in inflammation.
Eight SNPs in the CHI3L1 gene and promotor were genotyped in 308 patients with RA and 605 controls (healthy blood donors) using TaqMan allele discrimination assays. Serum concentrations of YKL-40 were determined by an enzyme-linked immunosorbent assay (ELISA).
We found significant association between the serum concentrations of YKL-40 and polymorphism in the CHI3L1 gene among both patients with RA and controls. The g.-131(C > G) polymorphism (rs4950928) was most strongly associated with age adjusted serum concentrations of YKL-40 in patients with RA (P < 2.4e-8) and controls (P < 2.2e-16). No significant allelic- or genotypic association with RA was found in this Danish cohort.
We suggest that the g.-131(C > G) promoter polymorphism has a substantial impact on serum concentrations of YKL-40 in patients with RA and healthy subjects. However, the polymorphism does not seem to confer risk to RA itself. The effect of CHI3L1 polymorphism on clinical outcome or the response to treatment in patients with RA remains to be investigated.