PPAR-g Gene Polymorphisms and Psoriatic Arthritis
CHRISTOPHER BUTT, DAFNA GLADMAN, and PROTON RAHMAN
Objective. Peroxisome proliferator-activated receptor-g (PPAR-g) activation has been shown to play a role in suppressing angiogenesis and inflammation, both important pathological features of psoriatic arthritis (PsA). Given the potential physiological role for PPAR-g in PsA, we examined known coding polymorphisms in the PPAR-g gene in a Caucasian population.
Methods. PsA was diagnosed as an inflammatory arthritis in patients with psoriasis, in the absence of other etiologies for inflammatory arthritis. Control subjects were ascertained from the same population and were all Caucasian. DNA samples were genotyped for 4 PPAR-g variants by time-of–flight mass spectrometry using the Sequenom platform. All 4 single-nucleotide polymorphisms (SNP) were previously-reported coding variations, 3 of which caused an amino acid change: Pro12Ala (rs1801282), Pro40Ala (rs1805192), and Pro115Gln (rs1800571); the fourth SNP, C161T (rs3856806), was synonymous. All primers were designed using Sequenom SpectroDesigner software, and scanned using a mass spectrometry workstation.
Results. Of the 4 SNP examined, Pro40Ala and Pro115Gln were found to be nonpolymorphic in our population. Minor allele frequency for patients with PsA and controls for Pro12Ala (G) were 9.0% vs 13.8% (p = 0.017) and for C161T (T) 10.7% vs 12.0% (p = 0.56), respectively. All genotypes satisfied Hardy-Weinberg equilibrium.
Conclusion. An association between PsA and a known coding SNP of the PPAR-g gene was observed in our Caucasian population. Further studies are now warranted for validation of our findings in an independent cohort. (First Release June 15 2006; J Rheumatol 2006;33:1631–3)
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From St. Clare's Mercy Hospital, Memorial University of Newfoundland, St. John's, Newfoundland; and Center for Prognosis Studies in Rheumatic Diseases, University Health Network, University of Toronto, Toronto, Ontario, Canada.
C. Butt, MSc, Graduate Student, Memorial University of Newfoundland; D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto, Director, Psoriatic Arthritis Program, Senior Scientist, Toronto Western Research Institute; P. Rahman, MD, MSc, FRCPC, Associate Professor of Medicine, Memorial University of Newfoundland.
Address reprint requests to Dr. P. Rahman, St. Clare's Mercy Hospital, 1 South, 154 LeMarchant Road, St. John's, Newfoundland A1C 5B8, Canada. E-mail:firstname.lastname@example.org
Accepted for publication March 6, 2006.