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

Direct link
High-density genotyping of STAT4 reveals multiple haplotypic associations with systemic lupus erythematosus in different racial groups
Show others and affiliations
2009 (English)In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 60, no 4, 1085-1095 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disorder, with complex etiology and a strong genetic component. Recently, gene products involved in the interferon pathway have been under intense investigation in terms of the pathogenesis of SLE. STAT-1 and STAT-4 are transcription factors that play key roles in the interferon and Th1 signaling pathways, making them attractive candidates for involvement in SLE susceptibility. METHODS: Fifty-six single-nucleotide polymorphisms (SNPs) across STAT1 and STAT4 on chromosome 2 were genotyped using the Illumina platform, as part of an extensive association study in a large collection of 9,923 lupus patients and control subjects from different racial groups. DNA samples were obtained from the peripheral blood of patients with SLE and control subjects. Principal components analyses and population-based case-control association analyses were performed, and the P values, false discovery rate q values, and odds ratios with 95% confidence intervals were calculated. RESULTS: We observed strong genetic associations with SLE and multiple SNPs located within STAT4 in different ethnic groups (Fisher's combined P = 7.02 x 10(-25)). In addition to strongly confirming the previously reported association in the third intronic region of this gene, we identified additional haplotypic association across STAT4 and, in particular, a common risk haplotype that is found in multiple racial groups. In contrast, only a relatively weak suggestive association was observed with STAT1, probably due to its proximity to STAT4. CONCLUSION: Our findings indicate that STAT4 is likely to be a crucial component in SLE pathogenesis in multiple racial groups. Knowledge of the functional effects of this association, when they are revealed, might improve our understanding of the disease and provide new therapeutic targets.

Place, publisher, year, edition, pages
2009. Vol. 60, no 4, 1085-1095 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-102308DOI: 10.1002/art.24387ISI: 000265152800022PubMedID: 19333953OAI: oai:DiVA.org:uu-102308DiVA: diva2:214623
Available from: 2009-05-06 Created: 2009-05-06 Last updated: 2010-08-02Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Alarcón-Riquelme, Marta E.
By organisation
Department of Genetics and Pathology
In the same journal
Arthritis and Rheumatism
Medical and Health Sciences

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: 119 hits
ReferencesLink to record
Permanent link

Direct link