Open AccessAssociation of a nonsynonymous single‐nucleotide polymorphism of matrix metalloproteinase 9 with giant cell arteritis
Author(s) -
RodríguezPla A.,
Beaty T. H.,
Savino P. J.,
Eagle R. C.,
Seo P.,
Soloski M. J.
Publication year - 2008
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.23457
Subject(s) - single nucleotide polymorphism , giant cell arteritis , genotype , biology , linkage disequilibrium , haplotype , snp , gastroenterology , genetics , allele frequency , allele , pathology , medicine , vasculitis , gene , disease
Objective Giant cell arteritis (GCA) is the most common type of primary vasculitis. Matrix metalloproteinase 9 (MMP‐9) is present in arterial lesions of GCA and may be involved in its pathogenesis. We investigated whether certain genotypes of 4 single‐nucleotide polymorphisms (SNPs) of MMP‐9 are overrepresented in patients with histologically confirmed GCA. Methods Four SNPs of MMP‐9, rs3918242 in the promoter region and 3 nonsynonymous coding SNPs (rs3918252, rs17576, and rs2250889) were genotyped by polymerase chain reaction–restriction fragment length polymorphism analysis in 58 white patients for whom there was a clinical suspicion of GCA. Thirty of these patients had histologically confirmed GCA (group 1), and 28 patients had negative results of a temporal artery biopsy for GCA (group 2). Estimates of the genotype distributions of each of these SNPs in a white population were determined using publicly available genotype data for a panel of 23 individuals (group 3). Results Although 1 SNP was monomorphic in all 3 groups, we observed statistically significant differences in the genotype distributions for rs2250889 between group 1 and group 2 ( P = 0.005) and between group 1 and group 3 ( P = 0.009), but not between groups 2 and 3 ( P = 0.965). Conclusion These data derived from a sample of patients with GCA suggest that the G allele of MMP‐9 polymorphism rs2250889 is overrepresented in patients with histologically confirmed GCA. Clearly, larger sample sizes will be necessary to confirm this suggestive association and better characterize a possible linkage disequilibrium structure among polymorphisms.