Association of an IRF5 gene functional polymorphism with Sjögren's syndrome.
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.


CONCLUSIONS
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.
Miceli-Richard
Corinne
C
INSERM U802, Université Paris-Sud 11, Hôpital Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France.
Comets
Emmanuelle
E
Loiseau
Pascale
P
Puechal
Xavier
X
Hachulla
Eric
E
Mariette
Xavier
X
D000483:Alleles; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012859:Sjogren's Syndrome / Q000235:genetics*
C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors