Trial reportStroke2011
Pharmacogenetic effect of the stromelysin (MMP3) polymorphism on stroke risk in relation to antihypertensive treatment: the genetics of hypertension associated treatment study.
Trial report in Stroke, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00563901 (GenHAT - Genetics of Hypertension Associated Treatments - Ancillary to ALLHAT), which is not on this map. Cited by 13 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
GenHAT - Genetics of Hypertension Associated Treatments - Ancillary to ALLHAT
Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Guideline
- The effects of genes implicated in cardiovascular disease on blood pressure response to treatment among treatment-naive hypertensive African Americans in the GenHAT study.Journal of human hypertension · 2016Trial
- Association of the antihypertensive response of iptakalim with KCNJ11 (Kir6.2 gene) polymorphisms in Chinese Han hypertensive patients.Acta pharmacologica Sinica · 2011Trial
- Pharmacogenetic association of theFrontiers in pharmacology · 2023Article
- The Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure (InterGEN) Study: Design and Methods for Complex DNA Analysis.Biological research for nursing · 2016Article
- The Role of Matrix Metalloproteinase Polymorphisms in Ischemic Stroke.International journal of molecular sciences · 2016Review
- The effect of gender and genetic polymorphisms on matrix metalloprotease (MMP) and tissue inhibitor (TIMP) plasma levels in different infectious and non-infectious conditions.Clinical and experimental immunology · 2015Article
- Genetic and Adverse Health Outcome Associations with Treatment Resistant Hypertension in GenHAT.International journal of hypertension · 2013Article
- Advancing management of hypertension through pharmacogenomics.Annals of medicine · 2012Review
- Cardiovascular pharmacogenomics.Circulation research · 2011Review
- Mutational analysis of the Kir6.1 gene in Chinese hypertensive patients treated with the novel ATP-sensitive potassium channel opener iptakalim.Experimental and therapeutic medicine · 2011Article
- Association Between Stress and Coping with DNA Methylation of Blood Pressure-Related Genes Among African American Women.Chronic stress (Thousand Oaks, Calif.)Article
- Exploring Cytokine Networks in Resistant Hypertension.Nursing researchArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
background and purposeAtherothrombotic diseases including stroke share a common etiology of atherosclerosis, and susceptibility to atherosclerosis has a genetic component. Stromelysin-1 (matrix metalloproteinase-3 [MMP3]) regulates arterial matrix composition and is a candidate gene for atherothrombosis. A common polymorphism of MMP3 alters expression levels and affects atherosclerotic progression and plaque stability. As part of the Genetics of Hypertension Associated Treatment study, ancillary to the Antihypertensive and Lipid Lowering to Prevent Heart Attack Trial, we evaluated the 5A/6A polymorphism in MMP3 to determine its association with stroke and determine whether it modifies clinical outcome response to blood pressure-lowering drugs.
methodsThe effect of the MMP3 5A/6A polymorphism on stroke rates was examined by using multivariate-adjusted Cox regression models, including a test for interactions between genotype and antihypertensive drug class.
resultsCompared with participants treated with chlorthalidone with the 6A/6A genotype, individuals with the 6A/6A genotype randomized to lisinopril had higher stroke rates (hazard ratio=1.32; 95% CI, 1.08 to 1.61; P=0.007) and 5A/6A individuals taking lisinopril had lower stroke rates (hazard ratio(interaction)=0.74; 95% CI, 0.53 to 1.04; P(interaction)=0.08), whereas 5A/5A individuals taking lisinopril had the lowest stroke rate (hazard ratio(interaction)=0.51; 95% CI, 0.31 to 0.85; P(interaction)=0.009). There were no pharmacogenetic differences in stroke rate by genotype in patients taking amlodipine or doxazosin vs chlorthalidone.
conclusionsThe MMP3 6A/6A genotype is associated with an increased risk of stroke in hypertensive subjects taking lisinopril compared with patients treated with chlorthalidone, whereas a protective effect was found for 5A/5A individuals treated with lisinopril. Genetic screening for the MMP3 5A/6A genotype might be a useful tool to select optimal antihypertensive therapy if this finding is replicated. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00563901.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.