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No evidence of association between genetic variants of the PDCD1 ligands and SLE
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2007 (English)In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 8, no 1, 69-74 p.Article in journal (Refereed) Published
Abstract [en]

PDCD1, an immunoreceptor involved in peripheral tolerance has previously been shown to be genetically associated with systemic lupus erythematosus (SLE). PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24. Our attention was drawn to these ligands after finding suggestive linkage to a marker (gata62f03, Z=2.27) located close to their genes in a genome scan of Icelandic families multiplex for SLE. Here, we analyse Swedish trios (N=149) for 23 single nucleotide polymorphisms (SNPs) within the genes of the PDCD1 ligands. Initially, indication of association to eight SNPs was observed, and these SNPs were therefore also analysed in Mexican trios (N=90), as well as independent sets of patients and controls from Sweden (152 patients, 448 controls) and Argentina (288 patients, 288 controls). We do not find support for genetic association to SLE. This is the first genetic study of SLE and the PDCD1 ligands and the lack of association in several cohorts implies that these genes are not major risk factors for SLE.

Place, publisher, year, edition, pages
2007. Vol. 8, no 1, 69-74 p.
Keyword [en]
systemic lupus erythematosus, genetic association, linkage disequilibrium, autoimmunity, PD-L1, PD-L2
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-97760DOI: 10.1038/sj.gene.6364360ISI: 000243783500009PubMedID: 17136123OAI: oai:DiVA.org:uu-97760DiVA: diva2:172820
Available from: 2008-11-14 Created: 2008-11-14 Last updated: 2011-02-18Bibliographically approved
In thesis
1. Genetic Risk Factors for Systemic Lupus Erythematosus: From Candidate Genes to Functional Variants
Open this publication in new window or tab >>Genetic Risk Factors for Systemic Lupus Erythematosus: From Candidate Genes to Functional Variants
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this thesis has been to identify genetic variants that increase the susceptibility for Systemic Lupus Erythematosus (SLE), an autoimmune disease caused by a complex interplay between various genetic and environmental factors.

Five different candidate genes were selected through different strategies, and were analysed for association with SLE in an attempt to distinguish some of the underlying mechanisms of this disease. Two of these genes, PD-L1 and PD-L2, appeared not to contain any major risk factors for SLE in the analysed European and Latin American populations. In two other genes, CD24 and STAT4, there appeared to be population-specific effects. The A57V amino acid substitution in the CD24 gene, previously implicated with multiple sclerosis, was associated in a Spanish cohort, with a weak trend in German samples, and no association in Swedish. The previously reported and highly convincing association of the STAT4 transcription factor gene was confirmed in all our cohorts. Interestingly, the results indicate the presence of at least two independent risk variants: the first, represented by a previously reported SNP, was the strongest in individuals of Northern European ancestry, and the second was more pronounced in individuals from Southern Europe and Latin America. We also report the identification of a novel susceptibility gene. The BANK1 gene, encoding a scaffold protein involved in B-cell activation, contains functional variants affecting important domains, which are associated in all investigated cohorts from Europe and Latin America.

These results confirm the existence of replicable associations between genetic variants and SLE, which are common and present in many populations. The results also illustrate a certain degree of heterogeneity, where some risk factors could have variable effect in different populations.

Place, publisher, year, edition, pages
Uppsala: Universitetsbiblioteket, 2008. 61 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 395
Keyword
Systemic Lupus Erythematosus, SLE, association study, complex disease, genetic
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-9367 (URN)978-91-554-7336-5 (ISBN)
Public defence
2008-12-06, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjölds väg 20, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2008-11-14 Created: 2008-11-14 Last updated: 2009-10-14Bibliographically approved

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Abelson, Anna-KarinKozyrev, Sergey V.Kristjansdottir, HelgaAlarcón-Riquelme, Marta E.

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