Osteopontin promoter polymorphism is associated with increased carotid intima-media thickness.
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.


CONCLUSIONS
Humans with the OPN -66 TT genotype, particularly those without metabolic syndrome, exhibit thicker CIMT.
de las Fuentes
Lisa
L
Cardiovascular Imaging and Clinical Research Core Laboratory, Cardiovascular Division, Washington University School of Medicine, St Louis, MO 63110, USA. lfuentes@wustl.edu
Gu
C Charles
CC
Mathews
Santhosh J
SJ
Reagan
Joann L
JL
Ruthmann
Nicholas P
NP
Waggoner
Alan D
AD
Lai
Chung-Fang
CF
Towler
Dwight A
DA
Dávila-Román
Víctor G
VG
D002339:Carotid Arteries / Q000000981:diagnostic imaging*; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008923:Missouri / Q000453:epidemiology; D053495:Osteopontin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D014463:Ultrasonography
D053495:Osteopontin