uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Preferential Association of Interferon Regulatory Factor 5 Gene Variants with Seronegative Rheumatoid Arthritis in 2 Swedish Case-Control Studies
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
Show others and affiliations
2011 (English)In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 38, no 10, 2130-2132 p.Article in journal (Refereed) Published
Abstract [en]


Two interferon regulatory factor 5 (IRF5) gene variants were examined for association with rheumatoid arthritis (RA).


A total of 2300 patients with RA and 1836 controls were recruited from 2 independent RA studies in Sweden. One insertion-deletion polymorphism (CGGGG indel) and one single-nucleotide polymorphism (rs10488631) in the IRF5 gene were genotyped and analyzed within RA subgroups stratified by rheumatoid factor (RF) and anticitrullinated peptide antibodies (ACPA).


The CGGGG indel was preferentially associated with the RF-negative (OR 1.29, p = 7.9 × 10−5) and ACPA-negative (OR 1.27, p = 7.3 × 10−5) RA subgroups compared to the seropositive counterparts. rs10488631 was exclusively associated within the seronegative RA subgroups (RF-negative: OR 1.24, p = 0.016; ACPA-negative: OR 1.27, p = 4.1 × 10−3).


Both the CGGGG indel and rs10488631 are relevant for RA susceptibility, especially for seronegative RA.

Place, publisher, year, edition, pages
2011. Vol. 38, no 10, 2130-2132 p.
Keyword [en]
rheumatoid arthritis, interferon regulatory factor 5, genetic association study, seronegative
National Category
Medical Genetics
URN: urn:nbn:se:uu:diva-162381DOI: 10.3899/jrheum.110322ISI: 000296545400008PubMedID: 21807777OAI: oai:DiVA.org:uu-162381DiVA: diva2:460452
Available from: 2011-11-30 Created: 2011-11-30 Last updated: 2014-08-14Bibliographically approved
In thesis
1. DNA Sequence Variants in Human Autoimmune Diseases
Open this publication in new window or tab >>DNA Sequence Variants in Human Autoimmune Diseases
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Human autoimmune diseases are hallmarked by inappropriate loss-of-tolerance and self-attacking response of the immune system. Studies included in this thesis are focusing on the implication and functional impact of genetic factors in three autoimmune diseases rheumatoid arthritis (RA), asthma, and systemic lupus erythematosus (SLE).

Using genetic association studies, we found in study I and II that sequence variants of the interferon regulatory factor 5 (IRF5) gene were associated with RA and asthma, and the associations were more pronounced in certain disease subtypes. Distinct association patterns or risk alleles of the IRF5 gene variants were revealed in different diseases, indicating that IRF5 contributes to disease manifestations in a dose-dependent manner. In study III, we found that seven out of eight genetic risk loci for SLE, which were originally identified in East Asian populations, also conferred disease risk with the same risk alleles and comparable magnitudes of effect sizes in Caucasians. Remarkable differences in risk allele frequencies were observed for all associated loci across ethnicities, which seems to be the major source of genetic heterogeneity for SLE. In study IV we explored an exhaustive spectrum of sequence variants in the genes inhibitor of kappa light polypeptide gene enhancer in B-cells kinase epsilon (IKBKE) and interferon induced with helicase C domain 1 (IFIH1) by gene resequencing, and identified nine variants in IKBKE and three variants in IFIH1 as genetic risk factors for SLE. One of the associated variants may influence splicing of IKBKE mRNA. In study V we provided genome-wide transcriptional regulatory profiles for IRF5 and signal transducer and activator of transcription 4 (STAT4) using chromatin immunoprecipitation-sequencing (ChIP-seq). The target genes of IRF5 and STAT4 were found to play active roles in pathways related with inflammatory response, and their expression patterns were characteristic for SLE patients. We also identified potential cooperative transcription factors for IRF5 and STAT4, and disease-associated sequence variants which may affect the regulatory function of IRF5 and STAT4.

In conclusion, this thesis illuminates the contribution of several genetic risk factors to susceptibility of human autoimmune diseases, which facilitates our understanding of the genetic basis of their pathogenesis.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 61 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 808
Association study, Gene resequencing, ChIP-seq, Type I interferon system, Systemic lupus erythematosus, Rheumatoid arthritis, Asthma
National Category
Medical and Health Sciences
Research subject
Medical Genetics; Molecular Genetics
urn:nbn:se:uu:diva-179189 (URN)978-91-554-8459-0 (ISBN)
Public defence
2012-10-18, Enghoffsalen, University Hospital, Entrance 50, Ground Floor, Uppsala, 09:15 (English)
Available from: 2012-09-27 Created: 2012-08-09 Last updated: 2013-01-23Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Wang, ChuanSandling, Johanna K.Syvänen, Ann-Christine
By organisation
Molecular Medicine
In the same journal
Journal of Rheumatology
Medical Genetics

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 243 hits
ReferencesLink to record
Permanent link

Direct link