Memorial University of Newfoundland, 1 Genetics and Genomic Biology, Hospital for Sick Children, Department of Public Health Sciences, University of Toronto, 2 Toronto Western Hospital, University of Toronto, Canada
Correspondence to: P. Rahman, St Clare's Mercy Hospital, 1 South154 LeMarchant Rd, St John's, Newfoundland, Canada A1C5B8. E-mail: prahman{at}mun.ca
SIR, Psoriatic arthritis (PsA) is an inflammatory arthritis associated with various extra-articular features, including psoriasis (which is seen in the majority of subjects with PsA) and, occasionally, inflammatory bowel disease. Recently, there have been major advances in the genetics of psoriasis (SLC9A3R1) [1], rheumatoid arthritis (SLC22A4 and RUNX1) [2], and Crohn's disease (a haplotype of SNPs in SLC22A4 and SLC22A5) [3]. As SLC22A4, SLC22A5, SLC9A3R1 and RUNX1 have a proposed role in chronic inflammatory disease, we set out to examine the association of these genes with PsA in the Newfoundland founder population.
This study was approved by the local ethics committee at Memorial University of Newfoundland. Informed consent was obtained from all PsA patients, who were all from the Newfoundland founder population. PsA was diagnosed as an inflammatory arthritis in patients with psoriasis, in the absence of other aetiologies for inflammatory arthritis. The control subjects were also ascertained from Newfoundland and were all unrelated.
All subjects were genotyped for three SNPs in SLC22A4 (rs3792876, 1050152, rs3763112), one SNP in SLC22A5 (rs2631367), one SNP in SLC9A3R1 (rs734232), and one SNP in RUNX1 (rs2268277) using the Sequenom MassArray platform using time-of-flight mass spectrometry (Sequenom, Inc., San Diego, CA).
2 analysis was used to test the single locus associations between SNPs in our selected candidate genes and PsA. Associations between multilocus haplotypes and case or control status were tested using the PHASE software, version 2.1 (http://www.stat.washington.edu/stephens/software.html).
Two hundred and fifty-nine PsA probands and 238 ethnically matched controls were studied. All subjects were Caucasian of north European descent and considered to be native Newfoundlanders. The mean age of PsA patients at the time of study was 49.67 yr (S.D. 10.95 yr), and 48.5% of the subjects were females. The mean age of onset of psoriasis in our cohort was 29.27 yr (S.D. 14.16 yr). Overall, 98% of the samples were genotyped successfully, and all of the genotypes for the controls satisfied the HardyWeinberg equilibrium.
With respect to single locus associations, none of the variants examined from SLC22A4, SLC22A5, SLC9A3R1 and RUNX1 were significantly associated with PsA in the Newfoundland population either by genotype or minor allele frequencies (Table 1).
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Thus in our study, we noted no association between the organic cation transporter genes and PsA in the Newfoundland population. This is in contrast to a recent British study that investigated 471 Caucasian PsA patients and 605 population controls for similar variants in SLC22A4 and SLC22A5 [4]. They noted two SNPs, rs3763112 mapping to SLC22A4 and rs2631367 mapping to SLC22A5, to be significantly associated with PsA (P = 0.001 and P = 0.007, respectively). Furthermore, the same haplotype as Crohn's disease between SNPs (rs1050152 and rs2631367) was strongly associated with PsA (P = 0.0002) in their population. The lack of association of these SNPs and the Crohn's disease haplotype in our study may reflect a difference in the PsA populations, as Newfoundland is a homogeneous founder Caucasian population, while the British population was admixed. A potential benefit of studying the Newfoundland population is the possibility of an amplified genotype relative risk due to the enhanced signal to noise ratio that exists in the population as a result of genetic and relative environmental homogeneity. However, as locus homogeneity is also likely to exist in the Newfoundland population, not all genes of potential importance to PsA will be implicated in the Newfoundland population. We also cannot rule out the possibility that an association exists for other SNPs within these genes, or to other recently described organic cation transporter genes in the IBD5 locus (OCTN3) [5]. Furthermore, we also acknowledge that because our sample size is modest we are thus unlikely to detect small differences in allele frequencies.
With respect to the SLC9A3R1 gene, although this gene has a plausible biological role in psoriasis as it is expressed in polarized epithelial cells, we found no association between the variant of SLC9A3R1 examined and PsA in the Newfoundland PsA population.
Therefore we were unable to implicate SLC22A4, SLC22A5, SLC9A3R1 and RUNX1 in the Newfoundland PsA population, even though there is significant epidemiological, clinical and immunological overlap between PsA, psoriasis, rheumatoid arthritis and Crohn's disease.
The authors have declared no conflicts of interest.
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