Objective. To study the linkage and association of ankylosing spondylitis (AS) with genotypes for matrix metalloproteinase 3 (MMP3), a gene located at chromosome 11q22.3 and lying within the 101-124 cM region observed in a recent genome-wide scan as a region associated with AS susceptibility. Methods. MMP3 genotypes were examined in 229 pedigrees with AS, 131 sporadic AS cases and 87 Caucasian controls. Eight single-nucleotide polymorphisms (SNPs) were selected and genotyped using Taqman. Non-parametric linkage (NPL) analysis was conducted between the eight MMP3 SNPs and AS using the NPL-all statistic and two-point parametric linkage analysis using GeneHunter Plus. Unrelated AS cases and controls were compared using χ2 statistics, and family-based controls using the transmission disequilibrium test and pedigree disequilibrium test. Results. None of the eight MMP3 SNPs were significantly associated with AS, either using the 131 sporadic cases alone or in analyses which combined these cases with the 226 unrelated affected AS patients derived from the pedigrees. Analysis of linkage disequilibrium (LD) demonstrated that seven of the eight SNPs studied were in strong LD except for rs626750, which is about 6 kb upstream of the 5′ end of the gene. No significant linkage was observed using NPL and LODs in the families. No association was seen of any of the MMP3 SNPs with disease severity (defined by patient functioning), as measured either by the Bath Ankylosing Spondylitis Functional Index or the modified Health Assessment Questionnaire. Conclusion. These data suggest that MMP3 genotypes are not involved in AS susceptibility or severity.
Bibliographical noteFunding Information:
We would like to express our sincere appreciation to the families who participated in this study and have supported the NASC project, as well as to Patricia Newman and Myriam Bianco, the Clinical Coordinators for this study at the Spondylitis Association of American, who were responsible for the recruitment of many of the families in this study, and to Laura Diekman and Jo McClain at the University of Texas-Houston Health Science Center, the Program Manager for this project. This work was supported by NIH grants RO1-AR46208. Additional support was provided by a grant from the National Eye Institute-EY13139 (TM, principal investigator) as well as by University Clinical Research Center Grants M01-RR02558 (UTHSC) and M01RR000425 (Cedars-Sinai).
- Ankylosing spondylitis
- Disease severity
- Matrix metalloproteinase 3
- Single-nucleotide polymorphisms