Systematic candidate gene investigations in the SPA2 locus (9q32) show an association between TNFSF8 and susceptibility to spondylarthritis
| Autor: | Agathe Vigier, Elena Zinovieva, Maxime Breban, Fernando Pimentel-Santos, Dirk Elewaut, Nicolas Cagnard, Brigitte Izac, R. Said-Nahal, Kurt de Vlam, Amir Kadi, Gilles Chiocchia, Franck Letourneur |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Candidate gene Genotype Genetic Linkage Immunology Locus (genetics) Single-nucleotide polymorphism Polymorphism Single Nucleotide Rheumatology Spondylarthritis Odds Ratio Humans Immunology and Allergy Medicine SNP Genetic Predisposition to Disease Pharmacology (medical) Allele Alleles Genetic Association Studies Genetics business.industry Haplotype Odds ratio Middle Aged Haplotypes CD30 Ligand business |
| Zdroj: | Arthritis & Rheumatism. 63:1853-1859 |
| ISSN: | 0004-3591 |
| Popis: | Objective Our group previously identified a new susceptibility region linked to spondylarthritis (SpA) on chromosome 9q31–34. Fine mapping of this SPA2 locus allowed us to refine the peak of linkage to a 1.3-Mb interval. The objective of this study was to resequence most positional candidate genes lying in that region, to identify polymorphisms, and to examine their association with SpA. Methods Variants screening was performed in 30 independent patients with SpA from families with a high linkage score to the SPA2 locus and 30 control subjects. The coding regions, intron–exon boundaries, and 5′- and 3′-flanking regions of ZNF618, A1L4R1_HUMAN (AF495724), AMBP, KIF12, ORM1, ORM2, C9ORF91, ENSESTG000000230601, and TNFSF8 were resequenced to identify polymorphisms. Selected variants were genotyped in an extended French cohort (442 patients and 268 control subjects overall). Replication was performed in a combined Belgian and Portuguese cohort (433 patients and 299 control subjects). Results Variants screening allowed us to identify 98 polymorphisms, 5 of which were selected for further studies, based on statistical significance. The rare intronic single-nucleotide polymorphism (SNP) rs3181357, located in TNFSF8, was significantly associated with SpA in the French and the replication cohorts (odds ratio [OR] 2.03, P = 0.009 and OR 2.26, P = 0.0014, respectively) and in the pooled analysis (OR 2.14, P = 0.0001). Conclusion Positional candidate gene screening in the SPA2 locus allowed us to identify and replicate an association between a rare SNP located in TNFSF8 and SpA. This new finding appears to be independent of an association with a haplotype near TNFSF15, which we recently reported. |
| Databáze: | OpenAIRE |
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