ASSOCIATION OF MSX-2 VARIANTS AND ANKYLOSING SPONDYLITIS

Background: Association of MSX-2 gene polymorphisms with AS has been recently reported in a Japanese population (1). MSX-2 is a transcription factor involved in bone development and ectopic calcification. In humans a loss of function mutation in MSX-2 causes defective skull ossification while gain of function mutation results in craniosynostosis. Objectives: Based on the previous association study and the role of MSX-2 in bone biology, we assessed 5 SNPs within the MSX-2 gene in a Canadian AS cohort. Methods: In total there were 1240 AS cases and 1958 controls, comprised from three AS centers in Canada (707 cases and 1098 controls from Alberta (AL); 385 cases and 498 controls from Toronto (TOR); 148 cases and 362 controls from Newfoundland (NL). Most AS patients were Caucasians of North European descent and satisfied the modified New York Classification Criteria. The healthy, unrelated controls were of similar ethnicity to the cases. Five SNPs were genotyped of which 4 were analyzed (see Table) as one marker did not satisfy H-W. Allele and haplotype associations were calculated using the WHAP software package. Given that 4 SNPs were tested, a Bonferroni correction will result in a 0.0125 p value cut-off. Results: The pooled analysis of all three Canadian cohorts revealed no evidence for a single marker associationmarker association of MSX-2 variants with AS (Table 1). However, a borderline association was noted in the Albertathe Alberta population for SNP rs4242182 (MAF for cases was 0.10 and for controls was 0.074; OR = 1.37; 95% CI 1.04-1.80, p = 0.027). Omnibus statistics revealed no overall haplotypic associations based on 3 markers for the pooled or individual samples. However the haplotype specific tests did reveal a significant association for the TCT haplotype from markers 1-2-3 in the Alberta (p=0.02) and pooled populations (p = 0.048). Table 1: Single marker analyses of MSX-2 variants in pooled AS MarkerAllelePooled casesPooled controlsPooled p-value rs6884071 (1)T0.380.380.91 rs7447819 (2)A0.290.300.42 rs4242182 (3)T0.090.080.21 rs4647949 (4)C0.440.430.48 Conclusion: Unlike the Japanese population there appears to be no convincing association between Canadian AS patients and selected variants of the MSX-2 gene. References: 1. Furuichi T. et al. J. Hum Genet 2008; 53:419-424 Disclosure of Interest: None declaredCitation: Annals of the Rheumatic Diseases, volume 68, supplement 3, year 2009, page 184Session: Genomics, genetic basis of disease and HLA/T cell recognition (Poster Presentations )