Genetic markers for PsA identified
MedWire News: Canadian research results confirm a previous association between a human leukocyte antigen (HLA) risk allele and psoriatic arthritis (PsA) and identify several further potential genetic markers for the condition among patients with psoriasis.
"The great challenge in investigating the genetics of PsA is related to the difficulty in differentiating the genes that confer a risk for the joint disease from those that are associated with the cutaneous disease" say Dafna Gladman, from Toronto Western Hospital in Ontario, and co-workers.
The team sought to identify HLA alleles that confer a PsA risk using data for 712 known PsA patients and 335 individuals with cutaneous psoriasis (PsC). DNA samples from 713 healthy controls were used for comparison.
DNA from participants' peripheral blood samples was analyzed for each of the HLA-A, HLA-B, HLA-C, and HLA-DQ loci. Previous research shows that the strongest associations with PsA lie within the HLA-B and HLA-C loci, therefore a single full logistic regression model of analysis was used for 10 alleles in these loci.
Three HLA alleles were significantly more frequent in the PsA versus PsC groups: HLA-B*27, HLA-C*01, and HLA-C*02.
Conversely, three alleles appeared significantly less frequently in PsA than PsC patients: HLA-C*06, HLA-B*57, and HLA-DRB1*07.
Multivariate analysis confirmed the association between PsA and HLA-B*27, the previously identified risk allele, revealing an odds ratio (OR) of 5.17.
The researchers suggest this allele can be considered as "the strongest risk allele for PsA among patients with PsC" in light of its known association with axial involvement, and earlier onset of joint manifestations in patients with PsC compared with noncarriers. They believe it ably differentiates the two conditions.
Analysis also showed that HLA-B*08 and HLA-B*38 were significantly more frequent in patients with PsA than those with PsC, and that HLA-B*27 and HLA-B*38 were significantly more frequent in patients with PsA compared with healthy controls.
In contrast, writes the research team in the Annals of Rheumatic Diseases, HLA-C*06 was significantly less frequent in the PsA group than in the PsC group (OR=0.58), but was significantly more frequent in the PsA group than in healthy controls (OR=1.71).
They add that the strong negative association between HLA-C*06 and PsC is hard to explain, suggesting that different HLA alleles could be associated with subtypes of psoriasis, ie, one allele for skin disease, and one for skin plus joint involvement.
The additional alleles with potential risk associations for PsA warrant further study, conclude Gladman et al.
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By Sarah Guy