ANKH and Susceptibility to and Severity of Ankylosing Spondylitis

• Published in: Journal of rheumatology Vol. 39; no. 1; pp. 131 - 134
• Main Authors: PIMENTEL-SANTOS, Fernando Manuel, LIGEIRO, Dario, CRUZ, Margarida, EURICO FONSECA, Joao, GUEDES-PINTO, Henrique, TRINDADE, Helder, BROWN, Matthew A, BRANCO, Jaime C, MATOS, Mafalda, FILIPA MOURAO, Ana, DE SOUSA, Elsa Vieira, PINTO, Patricia, RIBEIRO, Ana, SANTOS, Helena, BARCELOS, Anabela, GODINHO, Fatima
• Format: Journal Article
• Language: English
• Published: Toronto, ON Journal of Rheumatology Publishing 2012
• Subjects: Adult; Aged; Animals; Biological and medical sciences; Disease Susceptibility; Diseases of the osteoarticular system; Diseases of the spine; European Continental Ancestry Group - genetics; Female; Genetic Markers; Humans; Inflammatory joint diseases; Male; Medical sciences; Mice; Middle Aged; Phosphate Transport Proteins - genetics; Polymorphism, Single Nucleotide; Spondylitis, Ankylosing - genetics; Spondylitis, Ankylosing - pathology; Spondylitis, Ankylosing - physiopathology; Young Adult; Spondylarthropathy; Chronic; Prognosis; Diseases of the osteoarticular system; Rheumatology; Inflammatory joint disease; Spine disease; GENETIC PREDISPOSITION; Genetic determinism; Epidemiology; Morbidity; Ankylosing spondylitis
• ISSN: 0315-162X; 1499-2752
• DOI: 10.3899/jrheum.110681

Unconfirmed reports describe association of ankylosing spondylitis (AS) with several candidate genes including ANKH. Cellular export of inorganic pyrophosphate is regulated by the ANK protein, and mutant mice (ank/ank), which have a premature stop codon in the 3' end of the ank gene, develop severe ankylosis. We tested the association between single-nucleotide polymorphisms (SNP) in these genes and susceptibility to AS in a population of patients with AS. We investigated the role of these genes in terms of functional (BASFI) and metrological (BASMI) measures, and the association with radiological severity (mSASSS).
Our study was conducted on 355 patients with AS and 95 ethnically matched healthy controls. AS was defined according to the modified New York criteria. Four SNP in ANKH (rs27356, rs26307, rs25957, and rs28006) were genotyped. Association analysis was performed using Cochrane-Armitage and linear regression tests for dichotomous and quantitative variables. Analyses of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASFI, and mSASSS were controlled for sex and disease duration.
None of the 4 markers showed significant single-locus disease associations (p > 0.05), suggesting that ANKH was not a major determinant of AS susceptibility in our population. No association was observed between these SNP and age at symptom onset, BASDAI, BASFI, BASMI, or mSASSS.
These results confirm data in white Europeans that ANKH is probably not a major determinant of susceptibility to AS. ANKH polymorphisms do not markedly influence AS disease severity, as measured by BASMI and mSASSS.