doi: 10.1161/01.STR.0000015558.63492.B6
(Stroke. 2002;33:1420.)
© 2002 American Heart Association, Inc.
Research Report |
Carotid Intima-Media Thickness Is Associated With Allelic Variants of Stromelysin-1, Interleukin-6, and Hepatic Lipase Genes
The Northern Manhattan Prospective Cohort Study
From the Neurological Institute (T.R., M.S.E., J.P., B.B-A., R.L.S.) and Genome Center (S-H.H.J.), Columbia University, New York, NY, and Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Department of Medicine, Royal Free and University College London, Medical School, London, UK (S.M., S.E.H.).
Correspondence to Tanja Rundek, MD, PhD, Neurological Institute, Room 552, New York Presbyterian Hospital at Columbia University, 710 W 168th St, New York, NY 10032. E-mail tr89{at}columbia.edu
Abstract
Background and Purpose— Atherosclerosis is a complex disorder with hereditary and environmental causes. Carotid artery intima-media wall thickness (IMT) is a useful measure of atherosclerosis. The objective of this study was to determine the association between carotid IMT and functional promoter variants of stromelysin-1 (MMP3: -1612 5A>6A), interleukin-6 (IL6: -174G>C), and hepatic lipase (HL: -480C>T) genes.
Methods— B-mode carotid ultrasound was performed among 87 subjects (mean age, 70±12 years; 55% women; 60% Caribbean-Hispanic, 25% black, and 13% white) from the Northern Manhattan Prospective Cohort Study. Carotid IMT was calculated as a composite measure (mean of the maximum IMT in the bifurcation, the common carotid artery, and the internal carotid artery).
Results— For all polymorphisms, genotype distribution was not significantly different from Hardy-Weinberg equilibrium. The frequencies of the rare alleles were as follows: MMP3 -1612 5A>6A, 0.31 (95% CI, 0.25 to 0.39); IL6 -174 G>C, 0.20 (95% CI, 0.13 to 0.25); and HL -480 C>T, 0.45 (95% CI, 0.35 to 0.50). Carotid IMT in the sample was 0.78±0.18 mm. Subjects with the MMP3 genotype 6A6A had 8% greater mean carotid IMT than the other MMP3 genotypes combined (0.95±0.17 versus 0.87±0.15 mm; P=0.04). Subjects with the IL6 genotype GG had 11% greater IMT (0.85±0.17 versus 0.76±0.16 mm; P=0.03), and those with the HL genotype CC had 13% greater IMT (0.87±20 versus 0.76±0.18 mm; P=0.02) than the other genotypes combined. Adjustment for other risk factors did not change these associations.
Conclusions— Carotid IMT is higher among subjects homozygous for functional variants in genes related to matrix deposition (MMP3 -16126A), inflammation (IL6 -174G), and lipid metabolism (HL -480C). These associations were independent of race-ethnicity and some environmental exposures. Further studies are needed to confirm these genotype-phenotype associations.
Key Words: genetics • interleukin-6 • intima-media thickness • lipase • stromelysin 1 • ultrasonography
This article has been cited by other articles:
 |
|
 |
|
  M. D. Walker, J. Fleischer, T. Rundek, D. J. McMahon, S. Homma, R. Sacco, and S. J. Silverberg Carotid Vascular Abnormalities in Primary Hyperparathyroidism J. Clin. Endocrinol. Metab., October 1, 2009; 94(10): 3849 - 3856. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Cozzolino, M. L. Biondi, A. Galassi, O. Turri, D. Brancaccio, and M. Gallieni Matrix metalloproteinase-1 and matrix metalloproteinase-3 gene promoter polymorphisms are associated with mortality in haemodialysis patients Nephrol. Dial. Transplant., July 1, 2009; 24(7): 2207 - 2212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-C. Liao, H.-F. Lin, T. Rundek, R. Cheng, Y.-C. Guo, R. L. Sacco, and S.-H. H. Juo Segment-Specific Genetic Effects on Carotid Intima-Media Thickness: The Northern Manhattan Study Stroke, December 1, 2008; 39(12): 3159 - 3165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-C. Liao, J.-T. Lin, C.-Y. Wu, S.-P. Huang, M.-T. Lin, A. S.-H. Wu, Y.-J. Huang, and M.-S. Wu Serum Interleukin-6 Level but not Genotype Predicts Survival after Resection in Stages II and III Gastric Carcinoma Clin. Cancer Res., January 15, 2008; 14(2): 428 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Armstrong, S. Abilleira, M. Sitzer, H. S. Markus, and S. Bevan Polymorphisms in MMP Family and TIMP Genes and Carotid Artery Intima-Media Thickness Stroke, November 1, 2007; 38(11): 2895 - 2899. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Tso, J. G. Merino, and S. Warach Interleukin-6 174G/C Polymorphism and Ischemic Stroke: A Systematic Review Stroke, November 1, 2007; 38(11): 3070 - 3075. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Abilleira, S. Bevan, and H. S Markus The role of genetic variants of matrix metalloproteinases in coronary and carotid atherosclerosis J. Med. Genet., December 1, 2006; 43(12): 897 - 901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Prabhakaran, T. Rundek, R. Ramas, M. S.V. Elkind, M. C. Paik, B. Boden-Albala, and R. L. Sacco Carotid Plaque Surface Irregularity Predicts Ischemic Stroke: The Northern Manhattan Study Stroke, November 1, 2006; 37(11): 2696 - 2701. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yamada, N. Metoki, H. Yoshida, K. Satoh, S. Ichihara, K. Kato, T. Kameyama, K. Yokoi, H. Matsuo, T. Segawa, et al. Genetic Risk for Ischemic and Hemorrhagic Stroke Arterioscler Thromb Vasc Biol, August 1, 2006; 26(8): 1920 - 1925. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, Y. Berthier-Schaad, M. D. Fallin, N. E. Fink, R. P. Tracy, M. J. Klag, M. W. Smith, and J. Coresh IL-6 Haplotypes, Inflammation, and Risk for Cardiovascular Disease in a Multiethnic Dialysis Cohort J. Am. Soc. Nephrol., March 1, 2006; 17(3): 863 - 870. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ye Influence of matrix metalloproteinase genotype on cardiovascular disease susceptibility and outcome Cardiovasc Res, February 15, 2006; 69(3): 636 - 645. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P.S. Sie, F. A. Sayed-Tabatabaei, H.-H. S. Oei, A. G. Uitterlinden, H. A.P. Pols, A. Hofman, C. M. van Duijn, and J. C.M. Witteman Interleukin 6 -174 G/C Promoter Polymorphism and Risk of Coronary Heart Disease: Results from the Rotterdam Study and a Meta-Analysis Arterioscler Thromb Vasc Biol, January 1, 2006; 26(1): 212 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-H. H. Juo, T. Rundek, H.-F. Lin, R. Cheng, M.-Y. Lan, J. S. Huang, B. Boden-Albala, and R. L. Sacco Heritability of Carotid Artery Distensibility in Hispanics: The Northern Manhattan Family Study Stroke, November 1, 2005; 36(11): 2357 - 2361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Mayosi, P. J. Avery, M. Baker, N. Gaukrodger, H. Imrie, F. R. Green, M. Farrall, H. Watkins, and B. Keavney Genotype at the -174G/C Polymorphism of the Interleukin-6 Gene Is Associated With Common Carotid Artery Intimal-Medial Thickness: Family Study and Meta-Analysis Stroke, October 1, 2005; 36(10): 2215 - 2219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K P Burdon, C D Langefeld, S R Beck, L E Wagenknecht, J J Carr, B I Freedman, D Herrington, and D W Bowden Association of genes of lipid metabolism with measures of subclinical cardiovascular disease in the Diabetes Heart Study J. Med. Genet., September 1, 2005; 42(9): 720 - 724. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Hefler, C. Grimm, T. Lantzsch, D. Lampe, S. Leodolter, H. Koelbl, G. Heinze, A. Reinthaller, D. Tong-Cacsire, C. Tempfer, et al. Interleukin-1 and Interleukin-6 Gene Polymorphisms and the Risk of Breast Cancer in Caucasian Women Clin. Cancer Res., August 15, 2005; 11(16): 5718 - 5721. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-M. Fan, P. Dastidar, H. Jokela, R. Punnonen, and T. Lehtimaki Hepatic Lipase C-480T Genotype-Dependent Benefit from Long-Term Hormone Replacement Therapy for Atherosclerosis Progression in Postmenopausal Women J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3786 - 3792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Weger, I. Steinbrugger, A. Haas, W. Marz, Y. El-Shabrawi, W. Weger, O. Schmut, and W. Renner Role of the Interleukin-6 -174 G>C Gene Polymorphism in Retinal Artery Occlusion Stroke, February 1, 2005; 36(2): 249 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bennermo, C. Held, S. Stemme, C.-G. Ericsson, A. Silveira, F. Green, and P. Tornvall Genetic Predisposition of the Interleukin-6 Response to Inflammation: Implications for a Variety of Major Diseases? Clin. Chem., November 1, 2004; 50(11): 2136 - 2140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-H. H. Juo, H.-F. Lin, T. Rundek, E. A. Sabala, B. Boden-Albala, N. Park, M.-Y. Lan, and R. L. Sacco Genetic and Environmental Contributions to Carotid Intima-Media Thickness and Obesity Phenotypes in the Northern Manhattan Family Study Stroke, October 1, 2004; 35(10): 2243 - 2247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Pawlikowska, M. N. Tran, A. S. Achrol, C. E. McCulloch, C. Ha, D. L. Lind, T. Hashimoto, J. Zaroff, M. T. Lawton, D. A. Marchuk, et al. Polymorphisms in Genes Involved in Inflammatory and Angiogenic Pathways and the Risk of Hemorrhagic Presentation of Brain Arteriovenous Malformations Stroke, October 1, 2004; 35(10): 2294 - 2300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Manolio, E. Boerwinkle, C. J. O'Donnell, and A. F. Wilson Genetics of Ultrasonographic Carotid Atherosclerosis Arterioscler Thromb Vasc Biol, September 1, 2004; 24(9): 1567 - 1577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Doherty, L. A. Fitzpatrick, D. Inoue, J.-H. Qiao, M. C. Fishbein, R. C. Detrano, P. K. Shah, and T. B. Rajavashisth Molecular, Endocrine, and Genetic Mechanisms of Arterial Calcification Endocr. Rev., August 1, 2004; 25(4): 629 - 672. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Lanfear, S. Marsh, S. Cresci, W. D. Shannon, J. A. Spertus, and H. L. McLeod Genotypes associated with myocardial infarction risk are more common in African Americans than in European Americans J. Am. Coll. Cardiol., July 7, 2004; 44(1): 165 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Murase, Y. Yamada, A. Hirashiki, S. Ichihara, H. Kanda, M. Watarai, F. Takatsu, T. Murohara, and M. Yokota Genetic risk and gene-environment interaction in coronary artery spasm in Japanese men and women Eur. Heart J., June 1, 2004; 25(11): 970 - 977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Doherty, L. A. Fitzpatrick, A. Shaheen, T. B. Rajavashisth, and R. C. Detrano Genetic Determinants of Arterial Calcification Associated With Atherosclerosis Mayo Clin. Proc., February 1, 2004; 79(2): 197 - 210. [Abstract] [PDF]
|
|
|
|
|
|
A. Hirashiki, Y. Yamada, Y. Murase, Y. Suzuki, H. Kataoka, Y. Morimoto, T. Tajika, T. Murohara, and M. Yokota Association of gene polymorphisms with coronary artery disease in low- or high-risk subjects defined by conventional risk factors J. Am. Coll. Cardiol., October 15, 2003; 42(8): 1429 - 1437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M.L. Chapman, J. P. Beilby, S. E. Humphries, L. J. Palmer, P. L. Thompson, and J. Hung Association of an allelic variant of interleukin-6 with subclinical carotid atherosclerosis in an Australian community population Eur. Heart J., August 2, 2003; 24(16): 1494 - 1499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Beyzade, S. Zhang, Y.-k. Wong, I. N. M. Day, P. Eriksson, and S. Ye Influences of matrix metalloproteinase-3 gene variation on extent of coronary atherosclerosis and risk of myocardial infarction J. Am. Coll. Cardiol., June 18, 2003; 41(12): 2130 - 2137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Von der Thusen, J. Kuiper, T. J. C. Van Berkel, and E. A. L. Biessen Interleukins in Atherosclerosis: Molecular Pathways and Therapeutic Potential Pharmacol. Rev., March 1, 2003; 55(1): 133 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yamada, H. Izawa, S. Ichihara, F. Takatsu, H. Ishihara, H. Hirayama, T. Sone, M. Tanaka, and M. Yokota Prediction of the Risk of Myocardial Infarction from Polymorphisms in Candidate Genes N. Engl. J. Med., December 12, 2002; 347(24): 1916 - 1923. [Abstract] [Full Text] [PDF]
|
|