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Genetics of psoriasis and psoriatic arthritis: update and future direction.

ABSTRACT: Psoriasis and psoriatic arthritis (PsA) both have substantive genetic determinants. Numerous candidate regions and genes have now been replicated in disease susceptibility, and to a lesser extent in disease expression, in both disease entities. Intensive efforts are now under way or are being planned to perform genome-wide association scans (GWAS) in psoriasis and PsA. A major determinant of success for GWAS is likely to be accumulation of multiple large well-phenotyped cohorts, sophisticated data management, and verification of the findings. At the 2007 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members of the GRAPPA genetics committee presented a discussion of the genetics of psoriasis and PsA, including future trends. This article is a summary of that presentation and a review of the literature.

SUBMITTER: Duffin KC

PROVIDER: S-EPMC2724000 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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Genetics of psoriasis and psoriatic arthritis: update and future direction.

Duffin Kristina Callis KC Chandran Vinod V Gladman Dafna D DD Krueger Gerald G GG Elder James T JT Rahman Proton P

The Journal of rheumatology 20080701 7

Psoriasis and psoriatic arthritis (PsA) both have substantive genetic determinants. Numerous candidate regions and genes have now been replicated in disease susceptibility, and to a lesser extent in disease expression, in both disease entities. Intensive efforts are now under way or are being planned to perform genome-wide association scans (GWAS) in psoriasis and PsA. A major determinant of success for GWAS is likely to be accumulation of multiple large well-phenotyped cohorts, sophisticated da ...[more]

PMID: 18609743

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Project description:BackgroundOxylipins are biological lipids that have been implicated in inflammation. We previously found that certain oxylipins correlated with clinical manifestations in psoriatic arthritis (PsA) patients. Here, we compare oxylipin profiles in PsA patients and those with psoriasis (PsO) without inflammatory arthritis to identify oxylipins that associate with specific disease manifestations to better understand disease pathogenesis and identify new biomarkers.MethodsConsecutive patients with PsA (who met the CASPAR classification criteria for PsA) and PsO were recruited from the Rheumatology Outpatient Clinic. A thorough clinical examination was performed, including entheseal (Leeds enthesitis index (LEI)) and joint involvement (SJC/TJC 66/68). Patients were evaluated for pain and global disease activity on a visual analog scale (VAS) ranging from 0 to 100. This was followed by disease activity scores calculation: cDAPSA (Disease Activity Index for Psoriatic Arthritis) and Psoriasis Area and Severity Index (PASI). Serum oxylipins were determined by mass spectrometry and their association with clinical characteristics (PASI/LEI and cDAPSA) was analyzed using Metaboanalyst 4.0 and R version 3.6.1.ResultsTwenty PsO (average age 52 [10.8], 55% males) and 19 PsA patients (average age 60.5 [11.4], 63.1% males) were included. PsO patients had an average body mass index (BMI) of 33.7 (6.84) and an average PASI of 3.8 (4.2). PsA patients had an average BMI of 31.9 (5.6), TJC of 9.3 (10.41), SJC of 3.7 (4.23), with an average cDAPSA of 23.3 (11.4). 63.1% of PsA patients had enthesitis (average LEI 2.2 [3]) and the same percentage had psoriasis (average PASI 3(5]). Sera were analyzed for oxylipin levels. PsO and PsA patients with higher PASI score (> 2.5) had significantly lower serum concentrations of pro-inflammatory oxylipins, most of them arachidonic acid derived (AA). Oxylipin profiling did not associate with cDAPSA. Interestingly, several AA-derived oxylipins (5,15 di-HETE (5S,15S-dihydroxy-6E,8Z,10Z,13E-eicosatetraenoic acid), 5-oxoETE (5-Oxo-eicosatetraenoic acid), PGE2 (prostaglandin E2), 11bPGE2 (11 beta prostaglandin D2), and LTB4 (leukotriene B4)) were significantly increased in PsA patients with enthesitis compared to those without.ConclusionsThe AA-derived proinflammatory oxylipins were lower in both PsO and PsA patients with higher skin scores. Joint disease activity was not associated with the concentrations of oxylipins. Yet, enthesitis was associated with an increase of AA-derived pro-inflammatory oxylipins in PsA patients. Further studies are needed to determine whether oxylipin profiling can be a good biomarker of enthesitis in PsA patients.

Dataset Information

Genetics of psoriasis and psoriatic arthritis: update and future direction.

Publications

Genetics of psoriasis and psoriatic arthritis: update and future direction.

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