MMP-9 haplotypes and carotid artery atherosclerosis: an association study introducing a novel multicolour multiplex RealTime PCR protocol.
BACKGROUND
Among other matrix metalloproteinases (MMPs), gelatinase B (MMP-9) is discussed to be associated with the pathogenesis of vascular diseases. Two single nucleotide polymorphisms (SNPs) of the MMP-9 gene, C-1562T in the promoter region and a G/A transition in exon 6 (R + 279Q), have been addressed in previous association studies which, however, produced conflicting results.


METHODS
A novel multiplex RealTime PCR protocol for the fast and simultaneous detection of both polymorphisms is presented, which was used for genotyping 1737 participants of a prospective study investigating genetic factors influencing the progression of atherosclerosis.


RESULTS
Haplotype analysis revealed -1562C/+279Q as the major haplotype in this population. Allelic distribution of the C-1562T polymorphism was consistent with data published for similar cohorts; however, we found that R + 279Q allelic distribution appears to vary significantly among Caucasian populations. Considering clinical data available from 1487 participants, we found significant associations between the presence of atherosclerotic plaque and the CA-haplotype in men (P = 0.028, phi = 0.08), and between the AG variant of exon 6 and common carotid artery intima-media thickness (CIMT) in women (P = 0.004, Eta(2) = 0.019).


CONCLUSIONS
In summary, our results demonstrate associations of MMP-9 genotypes with different stages of carotid atherosclerosis.
Rauch
I
I
Department of Pediatrics, Paracelsus Medical University and Salzburger Landeskliniken, Salzburg, Austria.
Iglseder
B
B
Paulweber
B
B
Ladurner
G
G
Strasser
P
P
D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000000981:diagnostic imaging / Q000235:genetics*; D002340:Carotid Artery Diseases / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D014463:Ultrasonography
D020780:Matrix Metalloproteinase 9