Authors: C Enevold L Kjær C H Nielsen A Voss R S Jacobsen M L F Hermansen L Redder A B Oturai P E Jensen K Bendtzen S Jacobsen
Publish Date: 2014/04/10
Volume: 34, Issue: 10, Pages: 1401-1408
Abstract
This study aimed to demonstrate possible associations between genetic polymorphisms in Tolllike receptor 3 interferon induced with helicase C domain 1 IFIH1 and DEAD AspGluAlaAsp box polypeptide 58 and systemic lupus erythematosus SLE including the phenotypes lupus nephritis and malar rash as well as the presence of autoantibodies against nucleic acidcontaining complexes Genotyping was carried out in two Danish cohorts Copenhagen CPH and Odense ODE totaling 344 patients and was compared with 641 previously genotyped healthy controls In the ODE cohort the patients were only genotyped for the rs1990760 polymorphism of IFIH1 Single nucleotide polymorphisms SNPs were determined by a multiplex beadbased assay CPH cohort or realtime PCR ODE cohort Associations were investigated using the Cochran–Armitage Trend test The odds ratio OR for minor allele homozygotes versus major allele homozygotes suggested a protective effect of the IFIH1 rs1990760 SNP for SLE in the ODE cohort OR 052 95 confidence intervals 95 CI 031–088 Pcorr = 005 but not in the CPH cohort although the OR suggested a trend in the same direction and when combining the two patient cohorts ORs were 057 95 CI 037–088 None of the other investigated polymorphisms showed any association with SLE Regarding phenotypes we found a statistically significant association between rs1990760 and malar rash in the CPH cohort with ORs suggesting a protective effect OR 028 95 CI 013–062 for heterozygotes and OR 011 95 CI 003–041 for homozygotes Pcorr = 00001 There were no significant associations between rs1990760 and presence of antidsDNA antiU1RNP or antiSmith antibodies Our study supports previous findings of an association between the rs1990760 polymorphism of IFIH1 and SLE and indicates that this SNP may also be associated with malar rash in SLE patients although this finding needs confirmationThe authors thank Pia Grothe Meinke for technical assistance The authors also thank all patients and healthy control subjects for their participation The Danish Biotechnology Program The Novo Nordisk Foundation The Danish Rheumatism Association and The Lundbeck Foundation are thanked for financial support
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