St Clare's Mercy Hospital, Memorial University of Newfoundland, St John's, Newfoundland, 1 Center for Prognosis Studies in Rheumatic Diseases, University Health Network, University of Toronto, Toronto, Canada and 2 MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK
Correspondence to: P. Rahman, St Clare's Mercy Hospital, 1 South, 154 LeMarchant Rd, St John's, Newfoundland, Canada A1C 5B8. E-mail: prahman{at}mun.ca
SIR, Based on association studies and genome-wide linkage scans in psoriasis, there is convincing evidence for a major psoriasis susceptibility locus within the MHC complex (reviewed in [1]). The primary area of interest resides in a 200 kb region between HLA-C and corneodesmosin (CDSN) that is in strong linkage disequilibrium (LD). Despite widely reported associations between HLA-Cw0602 and psoriasis, there is ongoing debate about the role of HLA-Cw*0602 as the causative allele, as this allele is neither necessary nor sufficient for the development of psoriasis. Meanwhile, the CDSN gene, which is 160 kb from HLA-C, has been proposed as a candidate gene in psoriasis as it is the only PSORS1 transcript to be expressed in well-differentiated keratinocytes, and is responsible for corneocyte adhesion and desquamation [1]. However, association studies between CDSN and psoriasis have reported conflicting results and the data have been difficult to interpret due to LD with HLA-Cw6 [17]. The association between CDSN polymorphisms and psoriatic arthritis (PsA) has not been systematically evaluated. Thus, based on the inter-relationship between psoriasis and PsA, and the location and proposed function of CDSN, we examined the association between CDSN polymorphisms and PsA in two distinct populations, a founder population from Newfoundland, Canada, and an admixed population from Toronto, Canada.
This study was approved by the local ethics committees at Memorial University of Newfoundland and the University of Toronto. Informed consent was obtained from all patients according to the Declaration of Helsinki. PsA was diagnosed as an inflammatory arthritis in patients with psoriasis, in the absence of other aetiologies for inflammatory arthritis. The control subjects were ascertained from their respective regions, and were all unrelated.
Blood samples were collected from volunteers in EDTA anticoagulant and DNA was extracted from peripheral blood lymphocytes using the Wizard Genomic DNA Purification Kit (Promega, Madison, WI, USA). We evaluated the following four single-nucleotide polymorphisms in the CDSN gene: 619 (rs707913); 1215; 1236 (rs1042127); and 1243 (rs3132554). PsA subjects and controls were genotyped for the CDSN polymorphism by time-of-flight mass spectrometry, using the Sequenom platform. The PCR primers were designed using MassARRAY assay design software v1.3.4. Logistic regression was used to study the relationship between genotyping information and case/control status. The results are summarized in terms of significance tests.
We examined 226 PsA subjects and 107 controls from Newfoundland, and 210 PsA subjects and 99 controls from Toronto. The genotypes for the controls satisfied the HardyWeinberg equilibrium. The allele frequencies for PsA subjects and controls for CDSN polymorphisms in the Newfoundland and Toronto population are presented in Table 1. We observed no association between CDSN polymorphisms (619, 1215, 1236 and 1243) and PsA in either the Newfoundland or the Toronto cohort.
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In summary, we did not detect an association between CDSN polymorphisms and PsA in two distinct Canadian cohorts. However, the possibility remains that novel SNPs of these genes, or genes further up- or downstream of CDSN, may play a role in PsA. Alternatively, the CDSN may be in LD with the true susceptibility gene as a locus in a 70 kb interval around the CDSN gene has recently been mapped for psoriasis [9].
The authors have declared no conflicts of interest.
References
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