|(-;-)||5A/5A; higher MI risk?|
|(T;T)||6A/6A; higher CAD risk|
SNP rs3025058 was first described in 1995 as a variant upstream of, and influencing the regulation of, the MMP3 gene. Most commonly, the version of this SNP with a run of 5 A's is called the 5A allele, and an allele with 6 A's is called 6A. Thus, the homozygous genotypes are either 5A/5A or 6A/6A, and the heterozygote genotype is published as 5A/6A. Incidentally, the MMP3 gene is also called stromelysin-1, and although there is a SNP in dbSNP in the orientation that shows the polynucleotide run as A's (rs35068180) the entry that has population frequency data is the one discussed here, rs3025058, which is from the other strand and thus shows the string as T's.
There have been numerous studies in the last 10+ years linking either the 5A or 6A allele to risk for myocardial infarction or coronary artery disease. A relatively recent meta-analysis combining seven previously published studies concluded that the 5A allele is indeed a plaque-disrupting risk factor (odds ratio 1.26, CI: 1.1 - 1.4, p<0.001), while the 6A allele is associated with greater progression of coronary atherosclerosis and the 6A/6A genotype is associated with a worse progression of coronary artery disease after angioplasty. However, all these studies show a lot of heterogeneity, and gender, age, and ethnicity are all likely to alter the influence of these alleles. [PMID 16905683]
[PMID 19508478] no influence on varicose veins
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