rs3918242 — MMP9 MMP9 C-1562T

Promoter variant that disrupts an SP1 transcription factor binding site, increasing MMP-9 expression in vascular tissue; the T allele is associated with elevated plaque instability, higher risk of myocardial infarction, and increased ischemic stroke risk, particularly in Asian populations

See your personal result for MMP9

Upload your DNA data to find out which genotype you carry and what it means for you.

Upload your DNA data

Works with 23andMe, AncestryDNA, and other DNA test exports. Results in under 60 seconds.

MMP9 C-1562T — The Plaque-Destabilizing Promoter Variant

Your arteries are constantly remodeling. Smooth muscle cells, collagen fibers, and immune cells weave together to form atherosclerotic plaques — and whether those plaques stay stable or rupture depends heavily on the enzymes that digest the extracellular matrix. MMP-9 (matrix metalloproteinase 9) is one of the most destructive of these enzymes in the vascular wall. The rs3918242 C-1562T variant sits in the MMP9 promoter and controls how much of this enzyme your vascular cells produce.

The Mechanism

The C-to-T substitution at position −1562 in the MMP9 promoter disrupts an SP1 transcription factor binding site11 disrupts an SP1 transcription factor binding site
SP1 (specificity protein 1) is a zinc-finger transcription factor that normally suppresses MMP9 transcription when bound at this position. When the T allele is present, SP1 binding affinity is reduced, releasing the brakes on MMP9 expression. The result: higher baseline and inducible MMP-9 levels in vascular smooth muscle cells, macrophages, and endothelial cells.

MMP-9 is a gelatinase (also called gelatinase B) that digests type IV and V collagen, gelatin, and fibronectin — the structural scaffold of the fibrous cap that keeps atherosclerotic plaques stable. Elevated MMP-9 thins and weakens the fibrous cap, increasing the likelihood of sudden rupture. Plaque rupture is the proximate cause of most acute myocardial infarctions and many ischemic strokes. The gene sits on chromosome 20q11.21–13.12, and all alleles at this locus are reported on the plus (forward) strand, so C is the reference protective allele and T is the risk allele.

The Evidence

The largest meta-analysis, by Hassanzadeh-Makoui et al. (BMC Cardiovascular Disorders, 2020)22 Hassanzadeh-Makoui et al. (BMC Cardiovascular Disorders, 2020)
40 studies, 11,792 CAD cases and 8,280 controls, found the T allele conferred significant CAD risk under every genetic model: dominant OR 1.41, recessive OR 1.59, and TT vs. CC OR 1.70 (all P < 0.001). The effect was driven by Asian populations, with no significant association in Europeans.

An updated analysis by Zhang et al. (Oncotarget, 2017)33 Zhang et al. (Oncotarget, 2017)
37 studies, 24,407 total participants confirmed this pattern: overall CAD OR 1.34 (95% CI 1.20–1.50), rising to OR 1.66 for MI in Asian populations under the allelic model (OR 2.29 recessive). The modest effect in Europeans does not negate the biological plausibility — MMP-9 expression differences have been demonstrated in human coronary tissue regardless of ethnicity.

For stroke, a separate meta-analysis by Wang et al. (Journal of Cellular Biochemistry, 2018)44 Wang et al. (Journal of Cellular Biochemistry, 2018)
16 studies, 7,332 participants found the T allele increased stroke risk, particularly ischemic stroke in Asian populations.

In patients with type 2 diabetes, the risk is amplified: a study by Buraczynska et al. (Journal of Clinical Medicine, 2023)55 Buraczynska et al. (Journal of Clinical Medicine, 2023)
1,140 participants found CT/TT genotypes associated with CVD risk OR 2.87 for the T allele and OR 3.19 for TT homozygotes, with reduced HDL as a correlated finding.

Practical Actions

T allele carriers benefit from strategies that target MMP-9-driven plaque biology specifically: dietary approaches that reduce MMP-9 induction, monitoring that catches subclinical atherosclerosis early, and awareness of drug interactions that may modulate MMP-9 activity. Statins have documented MMP-9-suppressing effects at the transcriptional level — an additional reason for lipid management decisions in T allele carriers.

Interactions

The rs3918242 C-1562T variant interacts with the rs17576 (MMP9 Q279R) missense variant in the same gene. Studies have examined combined carriership of both polymorphisms in relation to coronary artery disease and plaque remodeling. Carriers of risk alleles at both positions may experience additive effects on MMP-9 activity — elevated expression from the promoter variant combined with altered substrate specificity from the coding variant. Interaction with rs2250889 (MMP9 R668Q) has also been reported in cardiovascular contexts. The supervisor agent should evaluate compound actions for co-carriership of rs3918242 T and rs17576 A alleles.

Genotype Interpretations

What each possible genotype means for this variant.

CC Normal

Normal MMP-9 promoter activity

You carry two copies of the C allele at the MMP9 promoter, which is the common protective variant. Your SP1 transcription factor binding at this site is intact, keeping baseline MMP-9 expression in the normal range. About 74% of people globally share this genotype. Population-level studies have not found an elevated risk of coronary artery disease or ischemic stroke associated with CC homozygosity.

CT Intermediate

One copy of the MMP-9-elevating T allele

The CT genotype is the most common risk-bearing configuration. Under the dominant model across multiple meta-analyses (>20,000 participants), CT carriers have statistically significant elevated CAD risk. The biological mechanism is a reduction in SP1-mediated suppression of MMP9 transcription: with only one normal C allele, repression of the promoter is incomplete, and MMP-9 levels in vascular tissue are elevated above baseline.

The clinical significance scales with overall cardiovascular risk burden. In individuals with additional risk factors — diabetes, dyslipidemia, hypertension, smoking — the elevated MMP-9 production from the T allele may meaningfully accelerate plaque destabilization. Measuring serum MMP-9 can confirm whether the genetic predisposition translates into elevated circulating enzyme levels in a given individual.

TT High Risk

Two copies of the MMP-9-elevating T allele — elevated plaque instability risk

The TT genotype represents the maximum promoter-driven MMP-9 expression state at this locus. With both alleles carrying the T substitution, SP1-mediated suppression of MMP9 transcription is eliminated at this site. Studies consistently show TT homozygotes have greater CAD and MI risk than CT heterozygotes, consistent with a codominant effect.

The principal mechanism is fibrous cap thinning: excess MMP-9 degrades the type IV collagen scaffold of the plaque fibrous cap. When the cap weakens, it can rupture under hemodynamic stress, exposing thrombogenic lipid core material and triggering platelet aggregation — the final trigger for acute MI or ischemic stroke.

Serum MMP-9 levels are measurable and correlate with cardiovascular event risk. TT carriers who also have elevated serum MMP-9 (>400 ng/mL) represent the highest-risk subgroup and benefit most from aggressive monitoring and pharmacological pleiotropic therapies such as statins, which suppress MMP-9 transcription through mevalonate pathway effects.