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Association of a CD24 Gene Polymorphism with Susceptibility to Systemic Lupus Erythematosus
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2007 (English)In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 56, no 9, 3080-3086 p.Article in journal (Refereed) Published
Abstract [en]

Objective. To determine the potential role of the CD24 A57V gene polymorphism in systemic lupus erythematosus (SLE).

Methods. We studied 3 cohorts of Caucasian patients and controls. The Spanish cohort included 696 SLE patients and 539 controls, the German cohort included 257 SLE patients and 317 controls, and the Swedish cohort included 310 SLE patients and 247 controls. The CD24 A57V polymorphism was genotyped by polymerase chain reaction, using a predeveloped TaqMan allele discrimination assay. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.

Results. In the Spanish cohort there was a statistically significant difference in the distribution of the CD24 V allele between SLE patients and controls (OR 3.6 [95% CI 2.13-6.16], P < 0.0001). In addition, frequency of the CD24 V/V genotype was increased in SLE patients compared with controls (OR 3.7 [95% CI 2.16-6.34], P < 0.00001). We sought to replicate this association with SLE in a German population and a Swedish population. A similar trend was found in the German group. The CD24 V/V genotype and the CD24 V allele were more frequent in SLE patients than in controls, although this difference was not statistically significant. No differences were observed in the Swedish group. A meta-analysis of the Spanish and German cohorts demonstrated that the CD24 V allele has a risk effect in SLE patients (pooled OR 1.25 [95% Cl 1.08-1.46], P = 0.003). In addition, homozygosity for the CD24 V risk allele significantly increased the effect (pooled OR 2.1,9 [95% Cl 1.50-3.22], P = 0.00007).

Conclusion. These findings suggest that the CD24 A57V polymorphism plays a role in susceptibility to SLE in a Spanish population.

Place, publisher, year, edition, pages
2007. Vol. 56, no 9, 3080-3086 p.
Keyword [en]
Antigens; CD24/*genetics, Cohort Studies, Female, Genetic Predisposition to Disease, Humans, Lupus Erythematosus; Systemic/*genetics, Male, Polymorphism; Genetic
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-97761DOI: 10.1002/art.22871ISI: 000249832600030PubMedID: 17763438OAI: oai:DiVA.org:uu-97761DiVA: diva2:172821
Available from: 2008-11-14 Created: 2008-11-14 Last updated: 2011-01-25Bibliographically 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.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 395
Systemic Lupus Erythematosus, SLE, association study, complex disease, genetic
National Category
Medical Genetics
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)
Available from: 2008-11-14 Created: 2008-11-14 Last updated: 2009-10-14Bibliographically approved

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