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.