Association of a nonsynonymous single-nucleotide polymorphism of matrix metalloproteinase 9 with giant cell arteritis.
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).


CONCLUSIONS
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.
Rodríguez-Pla
A
A
Johns Hopkins University School of Medicine, Baltimore, Maryland , USA. alirodriguez@humv.es
Beaty
T H
TH
Savino
P J
PJ
Eagle
R C
RC
Seo
P
P
Soloski
M J
MJ
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D013700:Giant Cell Arteritis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013699:Temporal Arteries / Q000473:pathology
D020780:Matrix Metalloproteinase 9