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Polymorphisms in MMP family and TIMP genes and carotid artery intima-media thickness.
Stroke 2007; 38(11):2895-9S

Abstract

BACKGROUND AND PURPOSE

Genetic variation in a number of MMP and TIMP genes have been implicated as risk factors for atherosclerosis, although such studies have been generally small and produced conflicting results. We have therefore sought to address this issue in a large, well-phenotyped community population to assess the effect of a number of polymorphisms in both MMP and TIMP genes on carotid artery intima-media thickness (IMT).

METHODS

In a community population (n=1000), IMT was determined using ultrasound in the common carotid artery, carotid bulb, and bifurcation. Eight polymorphisms in 6 MMP genes were genotyped (MMP1 A-519G, MMP2 C-1306T, MMP2 C-735T, MMP3 -1171 5A/6A, MMP9 R279Q, TIMP2 G853A, TIMP3 A-915G, and T-1296C) and assessed for their effect on carotid IMT alone and by interaction with common cardiovascular risk factors.

RESULTS

An association was found between MMP9 R279Q and internal carotid artery bulb IMT (P=0.002), but there was no linear trend between allele number and IMT and no association with common carotid artery or bulb IMT. In addition, 3 interactions were found between polymorphisms and hypertension (MMP1 A-519G, MMP3 5A/6A, TIMP3 T-1296C), the latter 2 of which showed a significant trend test for linearity with increasing copy number and increased internal carotid artery bulb IMT. All remained significant after correction for multiple testing.

CONCLUSIONS

Our findings provide little support for genetic variants of MMP as direct risk factors for IMT. However, the interaction findings between MMP variants and hypertension suggest that hypertensive carriers of these alleles may be at greater risk for increased IMT and future cardiovascular disease. These findings need replication in hypertensive populations to assess their effects more fully.

Authors+Show Affiliations

Centre for Clinical Neuroscience, St. George's University of London, Cranmer Terrace, Tooting, London, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17901377

Citation

Armstrong, Christine, et al. "Polymorphisms in MMP Family and TIMP Genes and Carotid Artery Intima-media Thickness." Stroke, vol. 38, no. 11, 2007, pp. 2895-9.
Armstrong C, Abilleira S, Sitzer M, et al. Polymorphisms in MMP family and TIMP genes and carotid artery intima-media thickness. Stroke. 2007;38(11):2895-9.
Armstrong, C., Abilleira, S., Sitzer, M., Markus, H. S., & Bevan, S. (2007). Polymorphisms in MMP family and TIMP genes and carotid artery intima-media thickness. Stroke, 38(11), pp. 2895-9.
Armstrong C, et al. Polymorphisms in MMP Family and TIMP Genes and Carotid Artery Intima-media Thickness. Stroke. 2007;38(11):2895-9. PubMed PMID: 17901377.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Polymorphisms in MMP family and TIMP genes and carotid artery intima-media thickness. AU - Armstrong,Christine, AU - Abilleira,Sonia, AU - Sitzer,Matthias, AU - Markus,Hugh S, AU - Bevan,Steve, Y1 - 2007/09/27/ PY - 2007/9/29/pubmed PY - 2007/12/6/medline PY - 2007/9/29/entrez SP - 2895 EP - 9 JF - Stroke JO - Stroke VL - 38 IS - 11 N2 - BACKGROUND AND PURPOSE: Genetic variation in a number of MMP and TIMP genes have been implicated as risk factors for atherosclerosis, although such studies have been generally small and produced conflicting results. We have therefore sought to address this issue in a large, well-phenotyped community population to assess the effect of a number of polymorphisms in both MMP and TIMP genes on carotid artery intima-media thickness (IMT). METHODS: In a community population (n=1000), IMT was determined using ultrasound in the common carotid artery, carotid bulb, and bifurcation. Eight polymorphisms in 6 MMP genes were genotyped (MMP1 A-519G, MMP2 C-1306T, MMP2 C-735T, MMP3 -1171 5A/6A, MMP9 R279Q, TIMP2 G853A, TIMP3 A-915G, and T-1296C) and assessed for their effect on carotid IMT alone and by interaction with common cardiovascular risk factors. RESULTS: An association was found between MMP9 R279Q and internal carotid artery bulb IMT (P=0.002), but there was no linear trend between allele number and IMT and no association with common carotid artery or bulb IMT. In addition, 3 interactions were found between polymorphisms and hypertension (MMP1 A-519G, MMP3 5A/6A, TIMP3 T-1296C), the latter 2 of which showed a significant trend test for linearity with increasing copy number and increased internal carotid artery bulb IMT. All remained significant after correction for multiple testing. CONCLUSIONS: Our findings provide little support for genetic variants of MMP as direct risk factors for IMT. However, the interaction findings between MMP variants and hypertension suggest that hypertensive carriers of these alleles may be at greater risk for increased IMT and future cardiovascular disease. These findings need replication in hypertensive populations to assess their effects more fully. SN - 1524-4628 UR - https://www.unboundmedicine.com/medline/citation/17901377/Polymorphisms_in_MMP_family_and_TIMP_genes_and_carotid_artery_intima_media_thickness_ L2 - http://www.ahajournals.org/doi/full/10.1161/STROKEAHA.107.491696?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -