Osteopontin Promoter Polymorphism Is Associated With Increased Carotid Intima-Media Thickness

Lisa de las Fuentes; C. Charles Gu; Santhosh J. Mathews; Joann L. Reagan; Nicholas P. Ruthmann; Alan D. Waggoner; Chung Fang Lai; Dwight A. Towler; Víctor G. Dávila-Román

doi:10.1016/j.echo.2008.02.005

Osteopontin Promoter Polymorphism Is Associated With Increased Carotid Intima-Media Thickness

Lisa de las Fuentes, C. Charles Gu, Santhosh J. Mathews, Joann L. Reagan, Nicholas P. Ruthmann, Alan D. Waggoner, Chung Fang Lai, Dwight A. Towler, Víctor G. Dávila-Román

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

Background: Osteopontin (OPN)-transgenic mice exhibit increased carotid artery intima-media thickness (CIMT), smooth muscle cell proliferation, and atheroma formation. Methods: An association of the human T-66G promoter variant with CIMT was examined in Caucasian adults grouped according to metabolic syndrome criteria: present (+MetS; n = 70) or absent (-MetS; n = 70). Results: The G-allele frequency was 22%. For the entire cohort, the G group (TG and GG) was associated with significantly lower age-adjusted and gender-adjusted CIMT compared with the TT group (P = .008); similar analysis by metabolic syndrome group found a significant difference only in the -MetS group (P = .018). Stepwise multivariate regression showed that after age and waist circumference, the T-66G variant was the next most predictive of CIMT (P = .007). These data suggest that in a normoglycemic environment, human vascular OPN gene expression contributes to arterial structure, an effect diminished in dysmetabolic states. Conclusion: Humans with the OPN -66 TT genotype, particularly those without metabolic syndrome, exhibit thicker CIMT.

Original language	English (US)
Pages (from-to)	954-960
Number of pages	7
Journal	Journal of the American Society of Echocardiography
Volume	21
Issue number	8
DOIs	https://doi.org/10.1016/j.echo.2008.02.005
State	Published - Aug 2008

Keywords

Arteriosclerosis
Carotid arteries
Genetics
Growth substances
Metabolic syndrome

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging
Cardiology and Cardiovascular Medicine

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10.1016/j.echo.2008.02.005

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@article{0c77cc009cfa4b19afcfd335f87681f1,

title = "Osteopontin Promoter Polymorphism Is Associated With Increased Carotid Intima-Media Thickness",

abstract = "Background: Osteopontin (OPN)-transgenic mice exhibit increased carotid artery intima-media thickness (CIMT), smooth muscle cell proliferation, and atheroma formation. Methods: An association of the human T-66G promoter variant with CIMT was examined in Caucasian adults grouped according to metabolic syndrome criteria: present (+MetS; n = 70) or absent (-MetS; n = 70). Results: The G-allele frequency was 22%. For the entire cohort, the G group (TG and GG) was associated with significantly lower age-adjusted and gender-adjusted CIMT compared with the TT group (P = .008); similar analysis by metabolic syndrome group found a significant difference only in the -MetS group (P = .018). Stepwise multivariate regression showed that after age and waist circumference, the T-66G variant was the next most predictive of CIMT (P = .007). These data suggest that in a normoglycemic environment, human vascular OPN gene expression contributes to arterial structure, an effect diminished in dysmetabolic states. Conclusion: Humans with the OPN -66 TT genotype, particularly those without metabolic syndrome, exhibit thicker CIMT.",

keywords = "Arteriosclerosis, Carotid arteries, Genetics, Growth substances, Metabolic syndrome",

author = "{de las Fuentes}, Lisa and Gu, {C. Charles} and Mathews, {Santhosh J.} and Reagan, {Joann L.} and Ruthmann, {Nicholas P.} and Waggoner, {Alan D.} and Lai, {Chung Fang} and Towler, {Dwight A.} and D{\'a}vila-Rom{\'a}n, {V{\'i}ctor G.}",

note = "Funding Information: This study was supported in part by National Institutes of Health grants K12RR023249 and KL2RR024994 (L.d.l.F), HL54473 (C.C.G.), R01HL69229 (D.A.T.), R01HL81138, R01HL71782, R01HL58878, K24HL67002, and P50Hl83762 (V.G.D.-R.), and M01RR00036 (General Clinical Research Center) (Washington University); Robert Wood Johnson Foundation grant 048875 (L.d.l.F); and a grant from the Barnes-Jewish Hospital Foundation to the Cardiovascular Imaging and Clinical Research Core Laboratory at the Washington University School of Medicine. ",

year = "2008",

month = aug,

doi = "10.1016/j.echo.2008.02.005",

language = "English (US)",

volume = "21",

pages = "954--960",

journal = "Journal of the American Society of Echocardiography",

issn = "0894-7317",

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number = "8",

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TY - JOUR

T1 - Osteopontin Promoter Polymorphism Is Associated With Increased Carotid Intima-Media Thickness

AU - de las Fuentes, Lisa

AU - Gu, C. Charles

AU - Mathews, Santhosh J.

AU - Reagan, Joann L.

AU - Ruthmann, Nicholas P.

AU - Waggoner, Alan D.

AU - Lai, Chung Fang

AU - Towler, Dwight A.

AU - Dávila-Román, Víctor G.

N1 - Funding Information: This study was supported in part by National Institutes of Health grants K12RR023249 and KL2RR024994 (L.d.l.F), HL54473 (C.C.G.), R01HL69229 (D.A.T.), R01HL81138, R01HL71782, R01HL58878, K24HL67002, and P50Hl83762 (V.G.D.-R.), and M01RR00036 (General Clinical Research Center) (Washington University); Robert Wood Johnson Foundation grant 048875 (L.d.l.F); and a grant from the Barnes-Jewish Hospital Foundation to the Cardiovascular Imaging and Clinical Research Core Laboratory at the Washington University School of Medicine.

PY - 2008/8

Y1 - 2008/8

N2 - Background: Osteopontin (OPN)-transgenic mice exhibit increased carotid artery intima-media thickness (CIMT), smooth muscle cell proliferation, and atheroma formation. Methods: An association of the human T-66G promoter variant with CIMT was examined in Caucasian adults grouped according to metabolic syndrome criteria: present (+MetS; n = 70) or absent (-MetS; n = 70). Results: The G-allele frequency was 22%. For the entire cohort, the G group (TG and GG) was associated with significantly lower age-adjusted and gender-adjusted CIMT compared with the TT group (P = .008); similar analysis by metabolic syndrome group found a significant difference only in the -MetS group (P = .018). Stepwise multivariate regression showed that after age and waist circumference, the T-66G variant was the next most predictive of CIMT (P = .007). These data suggest that in a normoglycemic environment, human vascular OPN gene expression contributes to arterial structure, an effect diminished in dysmetabolic states. Conclusion: Humans with the OPN -66 TT genotype, particularly those without metabolic syndrome, exhibit thicker CIMT.

AB - Background: Osteopontin (OPN)-transgenic mice exhibit increased carotid artery intima-media thickness (CIMT), smooth muscle cell proliferation, and atheroma formation. Methods: An association of the human T-66G promoter variant with CIMT was examined in Caucasian adults grouped according to metabolic syndrome criteria: present (+MetS; n = 70) or absent (-MetS; n = 70). Results: The G-allele frequency was 22%. For the entire cohort, the G group (TG and GG) was associated with significantly lower age-adjusted and gender-adjusted CIMT compared with the TT group (P = .008); similar analysis by metabolic syndrome group found a significant difference only in the -MetS group (P = .018). Stepwise multivariate regression showed that after age and waist circumference, the T-66G variant was the next most predictive of CIMT (P = .007). These data suggest that in a normoglycemic environment, human vascular OPN gene expression contributes to arterial structure, an effect diminished in dysmetabolic states. Conclusion: Humans with the OPN -66 TT genotype, particularly those without metabolic syndrome, exhibit thicker CIMT.

KW - Arteriosclerosis

KW - Carotid arteries

KW - Genetics

KW - Growth substances

KW - Metabolic syndrome

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U2 - 10.1016/j.echo.2008.02.005

DO - 10.1016/j.echo.2008.02.005

M3 - Article

C2 - 18406574

AN - SCOPUS:47649121931

SN - 0894-7317

VL - 21

SP - 954

EP - 960

JO - Journal of the American Society of Echocardiography

JF - Journal of the American Society of Echocardiography

IS - 8

ER -

Osteopontin Promoter Polymorphism Is Associated With Increased Carotid Intima-Media Thickness

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Keywords

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