OBJECTIVE: Interferon regulatory factor 5 (IRF-5) is a transcription factor involved in the regulation of the host defense. Previous studies have demonstrated a significant association of various IRF5 gene polymorphisms with systemic lupus erythematosus (SLE) in Caucasians. The purpose of this case-control study was to investigate whether IRF5 polymorphisms are involved in the genetic predisposition to primary Sjögren's syndrome (SS), an autoimmune disease closely related to SLE. METHODS: We analyzed IRF5 rs2004640, rs2070197, rs10954213, and rs2280714 polymorphisms in a cohort of 212 primary SS patients and 162 healthy blood donors, all of whom were of Caucasian origin. The 4 polymorphisms examined were genotyped by competitive allele-specific polymerase chain reaction using fluorescence resonance energy transfer technology. RESULTS: The IRF5 rs2004640 GT or TT genotype (T allele carriers) was identified in 87% of primary SS patients compared with 77% of controls (P = 0.01, odds ratio [OR] 1.93 [95% confidence interval (95% CI) 1.15-3.42]). The IRF5 rs2004640 T allele was found on 59% of chromosomes from primary SS patients compared with 52% of chromosomes from controls (P = 0.04, OR 1.36 [95% CI 1.01-1.83]). No significant association of primary SS with rs2070197, rs10954213, or rs2280714 was seen when they were analyzed independently. Nevertheless, haplotype reconstructions based on the 4 polymorphisms examined suggest that various allele combinations of rs2004640 and rs2070197 could define susceptibility or protective haplotypes. CONCLUSION: This study is the first to demonstrate a significant association between primary SS and the IRF5 rs2004640 T allele. These results, which require further replication on larger populations, suggest that besides their association with identical major histocompatibility complex gene polymorphisms, primary SS and SLE share IRF gene polymorphisms as a common genetic susceptibility factor.
OBJECTIVE:Interferon regulatory factor 5 (IRF-5) is a transcription factor involved in the regulation of the host defense. Previous studies have demonstrated a significant association of various IRF5 gene polymorphisms with systemic lupus erythematosus (SLE) in Caucasians. The purpose of this case-control study was to investigate whether IRF5 polymorphisms are involved in the genetic predisposition to primary Sjögren's syndrome (SS), an autoimmune disease closely related to SLE. METHODS: We analyzed IRF5rs2004640, rs2070197, rs10954213, and rs2280714 polymorphisms in a cohort of 212 primary SS patients and 162 healthy blood donors, all of whom were of Caucasian origin. The 4 polymorphisms examined were genotyped by competitive allele-specific polymerase chain reaction using fluorescence resonance energy transfer technology. RESULTS: The IRF5rs2004640 GT or TT genotype (T allele carriers) was identified in 87% of primary SS patients compared with 77% of controls (P = 0.01, odds ratio [OR] 1.93 [95% confidence interval (95% CI) 1.15-3.42]). The IRF5rs2004640 T allele was found on 59% of chromosomes from primary SS patients compared with 52% of chromosomes from controls (P = 0.04, OR 1.36 [95% CI 1.01-1.83]). No significant association of primary SS with rs2070197, rs10954213, or rs2280714 was seen when they were analyzed independently. Nevertheless, haplotype reconstructions based on the 4 polymorphisms examined suggest that various allele combinations of rs2004640 and rs2070197 could define susceptibility or protective haplotypes. CONCLUSION: This study is the first to demonstrate a significant association between primary SS and the IRF5rs2004640 T allele. These results, which require further replication on larger populations, suggest that besides their association with identical major histocompatibility complex gene polymorphisms, primary SS and SLE share IRF gene polymorphisms as a common genetic susceptibility factor.
Authors: M J Rood; M V van Krugten; E Zanelli; M W van der Linden; V Keijsers; G M Schreuder; W Verduyn; R G Westendorp; R R de Vries; F C Breedveld; C L Verweij; T W Huizinga Journal: Arthritis Rheum Date: 2000-01
Authors: Robert R Graham; Sergey V Kozyrev; Emily C Baechler; M V Prasad Linga Reddy; Robert M Plenge; Jason W Bauer; Ward A Ortmann; Thearith Koeuth; Ma Francisca González Escribano; Bernardo Pons-Estel; Michelle Petri; Mark Daly; Peter K Gregersen; Javier Martín; David Altshuler; Timothy W Behrens; Marta E Alarcón-Riquelme Journal: Nat Genet Date: 2006-04-16 Impact factor: 38.330
Authors: Snaevar Sigurdsson; Gunnel Nordmark; Harald H H Göring; Katarina Lindroos; Ann-Christin Wiman; Gunnar Sturfelt; Andreas Jönsen; Solbritt Rantapää-Dahlqvist; Bozena Möller; Juha Kere; Sari Koskenmies; Elisabeth Widén; Maija-Leena Eloranta; Heikki Julkunen; Helga Kristjansdottir; Kristjan Steinsson; Gunnar Alm; Lars Rönnblom; Ann-Christine Syvänen Journal: Am J Hum Genet Date: 2005-01-18 Impact factor: 11.025
Authors: Robert R Graham; Chieko Kyogoku; Snaevar Sigurdsson; Irina A Vlasova; Leela R L Davies; Emily C Baechler; Robert M Plenge; Thearith Koeuth; Ward A Ortmann; Geoffrey Hom; Jason W Bauer; Clarence Gillett; Noel Burtt; Deborah S Cunninghame Graham; Robert Onofrio; Michelle Petri; Iva Gunnarsson; Elisabet Svenungsson; Lars Rönnblom; Gunnel Nordmark; Peter K Gregersen; Kathy Moser; Patrick M Gaffney; Lindsey A Criswell; Timothy J Vyse; Ann-Christine Syvänen; Paul R Bohjanen; Mark J Daly; Timothy W Behrens; David Altshuler Journal: Proc Natl Acad Sci U S A Date: 2007-04-05 Impact factor: 11.205
Authors: Katrine Brække Norheim; Stephanie Le Hellard; Gunnel Nordmark; Erna Harboe; Lasse Gøransson; Johan G Brun; Marie Wahren-Herlenius; Roland Jonsson; Roald Omdal Journal: Rheumatol Int Date: 2013-09-03 Impact factor: 2.631
Authors: Barbara M Segal; Abu N M Nazmul-Hossain; Ketan Patel; Pamela Hughes; Kathy L Moser; Nelson L Rhodus Journal: Oral Surg Oral Med Oral Pathol Oral Radiol Endod Date: 2011-04-16
Authors: Thomas Krausgruber; Katrina Blazek; Tim Smallie; Saba Alzabin; Helen Lockstone; Natasha Sahgal; Tracy Hussell; Marc Feldmann; Irina A Udalova Journal: Nat Immunol Date: 2011-01-16 Impact factor: 25.606