OBJECTIVE: The interleukin-1 (IL-1) cytokine elicits a wide variety of biologic activities that initiate and promote an inflammatory response. The loci in the IL1 gene cluster have recently been associated with ankylosing spondylitis (AS). Since there is clinical and immunologic overlap between psoriatic arthritis (PsA) and AS, we wanted to examine the association between a panel of single-nucleotide polymorphisms (SNPs) in the IL1 gene family cluster and chromosome 2q12-13 in a PsA cohort. METHODS: Two hundred twelve PsA patients and 150 ethnically matched controls were genotyped with 11 SNPs in IL1A, 9 SNPs in IL1B, and 9 SNPs in IL1F5-10. Univariate analyses of the 29 single markers and short intragenic haplotypes identified several associated regions. Seventeen markers of interest were noted and further investigated to determine which markers or short haplotypes independently predict case-control status, using a stepwise logistic model. RESULTS; Two regions contributing independently to risk of disease in PsA were noted: a region spanned by markers rs3783547, rs3783543, and rs17561 in IL1A, and a region near the end of IL1B, through IL1F7, IL1F8, and into IL1F10. The best model contained markers rs3811047, rs1562304, and rs3811058, and 1 haplotype constructed from the 3 markers in region 1, with a likelihood ratio of 25.34 (4 degrees of freedom). CONCLUSION: The IL1 locus appears to be a high-priority susceptibility locus in PsA, with at least 2 independent regions that confer increased risk.
OBJECTIVE: The interleukin-1 (IL-1) cytokine elicits a wide variety of biologic activities that initiate and promote an inflammatory response. The loci in the IL1 gene cluster have recently been associated with ankylosing spondylitis (AS). Since there is clinical and immunologic overlap between psoriatic arthritis (PsA) and AS, we wanted to examine the association between a panel of single-nucleotide polymorphisms (SNPs) in the IL1 gene family cluster and chromosome 2q12-13 in a PsA cohort. METHODS: Two hundred twelve PsA patients and 150 ethnically matched controls were genotyped with 11 SNPs in IL1A, 9 SNPs in IL1B, and 9 SNPs in IL1F5-10. Univariate analyses of the 29 single markers and short intragenic haplotypes identified several associated regions. Seventeen markers of interest were noted and further investigated to determine which markers or short haplotypes independently predict case-control status, using a stepwise logistic model. RESULTS; Two regions contributing independently to risk of disease in PsA were noted: a region spanned by markers rs3783547, rs3783543, and rs17561 in IL1A, and a region near the end of IL1B, through IL1F7, IL1F8, and into IL1F10. The best model contained markers rs3811047, rs1562304, and rs3811058, and 1 haplotype constructed from the 3 markers in region 1, with a likelihood ratio of 25.34 (4 degrees of freedom). CONCLUSION: The IL1 locus appears to be a high-priority susceptibility locus in PsA, with at least 2 independent regions that confer increased risk.
Authors: Frank L van de Veerdonk; Angela K Stoeckman; Gouping Wu; Aaron N Boeckermann; Tania Azam; Mihai G Netea; Leo A B Joosten; Jos W M van der Meer; Ruyi Hao; Vassili Kalabokis; Charles A Dinarello Journal: Proc Natl Acad Sci U S A Date: 2012-02-06 Impact factor: 11.205
Authors: Alexandros Onoufriadis; Michael A Simpson; Andrew E Pink; Paola Di Meglio; Catherine H Smith; Venu Pullabhatla; Jo Knight; Sarah L Spain; Frank O Nestle; A David Burden; Francesca Capon; Richard C Trembath; Jonathan N Barker Journal: Am J Hum Genet Date: 2011-08-11 Impact factor: 11.025
Authors: Ivona Aksentijevich; Seth L Masters; Polly J Ferguson; Paul Dancey; Joost Frenkel; Annet van Royen-Kerkhoff; Ron Laxer; Ulf Tedgård; Edward W Cowen; Tuyet-Hang Pham; Matthew Booty; Jacob D Estes; Netanya G Sandler; Nicole Plass; Deborah L Stone; Maria L Turner; Suvimol Hill; John A Butman; Rayfel Schneider; Paul Babyn; Hatem I El-Shanti; Elena Pope; Karyl Barron; Xinyu Bing; Arian Laurence; Chyi-Chia R Lee; Dawn Chapelle; Gillian I Clarke; Kamal Ohson; Marc Nicholson; Massimo Gadina; Barbara Yang; Benjamin D Korman; Peter K Gregersen; P Martin van Hagen; A Elisabeth Hak; Marjan Huizing; Proton Rahman; Daniel C Douek; Elaine F Remmers; Daniel L Kastner; Raphaela Goldbach-Mansky Journal: N Engl J Med Date: 2009-06-04 Impact factor: 91.245