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H Kim, KL Edwards,
WT Longstreth, FM Farin, BM Psaty, AP Reiner, DS Siscovick, SM Schwartz,
University of Washington
Matrix metalloproteinases
(MMP) belong to a family of genes that code for enzymes that degrade
the extracellular matrix. Weakening of vessel walls caused by increased
MMP action could plausibly cause both ischemic and hemorrhagic strokes.
To examine the risk of stroke in young women in relation to putative
functional variants in the promoter region of MMP3 (5A/6A polymorphism)
and MMP9 (CA repeat polymorphism) genes, we analyzed samples from
a population-based case-control study in western Washington State.
Cases were women aged 18-44 years with nonfatal, incident strokes
(37 ischemic, 43 hemorrhagic). Demographically-similar controls
(n=224) were identified from the community by random-digit telephone
dialing. Unconditional logistic regression was used to analyze the
data; models were adjusted for age and restricted to Caucasians.
The frequency of the MMP3 5A allele was 53% for ischemic strokes,
44% for hemorrhagic strokes, and 53% for controls. The odds ratio
(OR) associated with the 5A allele was 0.80 [95% CI=0.34-1.89] for
ischemic strokes and 0.38 [0.18-0.77] for hemorrhagic strokes. We
observed twelve MMP9 alleles, ranging from 12 to 25 repeats. The
CA21 allele was more frequent in ischemic (22%) and hemorrhagic
(20%) stroke cases compared to controls (14%). ORs associated with
having any copy of the CA21 allele was 1.95 [0.93-4.06] for ischemic
strokes and 1.62 [0.80-3.28] for hemorrhagic strokes. Genotype frequencies
were not in Hardy-Weinberg equilibrium in controls for the MMP3
(p=0.023) or MMP9 (p=0.034) variants. In our population of young
Caucasian women, MMP3 and MMP9 appeared to be associated with risk
of stroke subtype.
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