Carotid intima-media thickness is associated with allelic variants of stromelysin-1, interleukin-6, and hepatic lipase genes: The Northern Manhattan Prospective Cohort Study

Tanja Rundek, Mitchell S. Elkind, John Pittman, Bernadette Boden-Albala, Steve Martin, Steve E. Humphries, Suh Hang Hank Juo, Ralph L. Sacco

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1420-1423
Number of pages4
JournalStroke
Volume33
Issue number5
DOIs
StatePublished - 2002

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Matrix Metalloproteinase 3
Carotid Intima-Media Thickness
Lipase
Interleukin-6
Cohort Studies
Genotype
Prospective Studies
Liver
Genes
Atherosclerosis
Common Carotid Artery
Environmental Exposure
Genetic Association Studies
Internal Carotid Artery
Lipid Metabolism
Carotid Arteries
Hispanic Americans
Gene Frequency
Inflammation

Keywords

  • Genetics
  • Interleukin-6
  • Intima-media thickness
  • Lipase
  • Stromelysin 1
  • Ultrasonography

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Carotid intima-media thickness is associated with allelic variants of stromelysin-1, interleukin-6, and hepatic lipase genes : The Northern Manhattan Prospective Cohort Study. / Rundek, Tanja; Elkind, Mitchell S.; Pittman, John; Boden-Albala, Bernadette; Martin, Steve; Humphries, Steve E.; Hank Juo, Suh Hang; Sacco, Ralph L.

In: Stroke, Vol. 33, No. 5, 2002, p. 1420-1423.

Research output: Contribution to journalArticle

Rundek, Tanja ; Elkind, Mitchell S. ; Pittman, John ; Boden-Albala, Bernadette ; Martin, Steve ; Humphries, Steve E. ; Hank Juo, Suh Hang ; Sacco, Ralph L. / Carotid intima-media thickness is associated with allelic variants of stromelysin-1, interleukin-6, and hepatic lipase genes : The Northern Manhattan Prospective Cohort Study. In: Stroke. 2002 ; Vol. 33, No. 5. pp. 1420-1423.
@article{d2dd1564488043c08f8109208126fda2,
title = "Carotid intima-media thickness is associated with allelic variants of stromelysin-1, interleukin-6, and hepatic lipase genes: The Northern Manhattan Prospective Cohort Study",
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.",
keywords = "Genetics, Interleukin-6, Intima-media thickness, Lipase, Stromelysin 1, Ultrasonography",
author = "Tanja Rundek and Elkind, {Mitchell S.} and John Pittman and Bernadette Boden-Albala and Steve Martin and Humphries, {Steve E.} and {Hank Juo}, {Suh Hang} and Sacco, {Ralph L.}",
year = "2002",
doi = "10.1161/01.STR.0000015558.63492.B6",
language = "English (US)",
volume = "33",
pages = "1420--1423",
journal = "Stroke",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Carotid intima-media thickness is associated with allelic variants of stromelysin-1, interleukin-6, and hepatic lipase genes

T2 - The Northern Manhattan Prospective Cohort Study

AU - Rundek, Tanja

AU - Elkind, Mitchell S.

AU - Pittman, John

AU - Boden-Albala, Bernadette

AU - Martin, Steve

AU - Humphries, Steve E.

AU - Hank Juo, Suh Hang

AU - Sacco, Ralph L.

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

KW - Genetics

KW - Interleukin-6

KW - Intima-media thickness

KW - Lipase

KW - Stromelysin 1

KW - Ultrasonography

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U2 - 10.1161/01.STR.0000015558.63492.B6

DO - 10.1161/01.STR.0000015558.63492.B6

M3 - Article

VL - 33

SP - 1420

EP - 1423

JO - Stroke

JF - Stroke

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