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. Conclusion: Humans with the OPN - 66 TT genotype, particularly those without metabolic syndrome, exhibit thicker CIMT.