Association of a single-nucleotide polymorphism inCD40with the rate of joint destruction in rheumatoid arthritis
| العنوان: | Association of a single-nucleotide polymorphism inCD40with the rate of joint destruction in rheumatoid arthritis |
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| المؤلفون: | Soumya Raychaudhuri, Monica Chang, Peter K. Gregersen, Jessica A B van Nies, René E. M. Toes, Fina A S Kurreeman, Saskia le Cessie, Anouk L. Feitsma, Marlena Kern, Joseph J. Catanese, Tom W J Huizinga, Désirée van der Heijde, Lina M. Olsson, Ann B. Begovich, Annette H M van der Helm-van Mil, Michael P M van der Linden |
| المصدر: | Arthritis & Rheumatism; Vol 60 |
| بيانات النشر: | Wiley, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Male, musculoskeletal diseases, Health Status, Inflammatory arthritis, Immunology, Arthritis, Single-nucleotide polymorphism, Peptides, Cyclic, Polymorphism, Single Nucleotide, Severity of Illness Index, TNFAIP3, Article, Arthritis, Rheumatoid, PTPN22, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, medicine, Humans, Immunology and Allergy, Genetic Predisposition to Disease, Pharmacology (medical), CD40 Antigens, Range of Motion, Articular, Allele, Arthrography, skin and connective tissue diseases, 030304 developmental biology, Genetic association, 030203 arthritis & rheumatology, 0303 health sciences, business.industry, Middle Aged, medicine.disease, 3. Good health, Rheumatoid arthritis, Female, Joints, business |
| الوصف: | Rheumatoid arthritis (RA) is characterized by inflammatory arthritis and localized destruction of bone and cartilage. The severity of joint destruction is highly variable between patients and, according to the findings of twin studies, substantially influenced by genetic factors (1). Nevertheless, the precise contribution of genetic factors has yet to be determined. To date, only a small number of genetic risk factors have been identified, and apart from HLA, the association of none of these factors with RA severity has been convincingly replicated. In contrast, the genetics of susceptibility to RA has been considerably boosted, largely due to the findings of genome-wide association studies. In addition to the HLA–DRB1 shared epitope alleles, several new susceptibility factors have been identified, and their association with RA has been independently replicated: PTPN22, TRAF1/C5, OLIG3/TNFAIP3, and STAT4. Intriguingly, for many of these genetic risk factors, the associations are confined to RA patients positive for anti–citrullinated protein antibody (ACPA). It remains unknown whether genetic factors also affect the severity of joint destruction in ACPA-positive and ACPA-negative RA in different ways. Nonetheless, compelling evidence demonstrates that ACPA-positive RA patients have a more destructive disease course than do ACPA-negative RA patients. A recent meta-analysis of 2 genome-wide association studies identified 6 new risk loci (rs4810485 [CD40], rs1678542 [KIF5A/PIP4K2C], rs42041 [CDK6], rs2812378 [CCL21], rs4750316 [PRKCQ], and rs3890745 [MMEL1/TNFRSF14]) as susceptibility factors for autoantibody-positive RA (2). In the present study, we investigated the association between these single-nucleotide polymorphisms (SNPs) and the rate of radiologic joint destruction in RA patients and in ACPA-positive RA in particular using a large longitudinal cohort. A cohort of ACPA-positive RA patients was used for replication analysis. We found that a genetic variant in the CD40 gene is associated with the rate of joint destruction in ACPA-positive RA patients. |
| تدمد: | 1529-0131 0004-3591 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::45db5118fcf5aa787159daa304b0632c https://doi.org/10.1002/art.24721 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....45db5118fcf5aa787159daa304b0632c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15290131 00043591 |
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