Phosphoprotein 1 (osteopontin) gene (rs4754) affects markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus.

ABSTRACT

BACKGROUND: Our study was designed to test a possible association between polymorphisms of the SPP1 gene (rs4754, rs28357094) and markers of carotid atherosclerosis (CIMT, number of affected segments of carotid arteries, sum of plaque thickness, presence of carotid plaques, and presence of unstable carotid plaques) in subjects with T2DM. The second aim was to test the possible association between polymorphisms of the SPP1 gene (rs4754, rs28357094) and the progression of carotid atherosclerosis (CIMT progression, change in total plaque thickness, change in the number of sites with plaques) in subjects with T2DM. METHODS: In the prospective study 595 T2DM subjects were enrolled. Markers of carotid atherosclerosis were assessed ultrasonographically. rs4754 and rs28357094 polymorphisms of the phosphoprotein 1 (SPP1) gene were determined with real-time PCR. RESULTS: In our study we found an association between SPP1 rs4754 and the presence of plaques at the time of recruitment, whereas we did not find any association between SPP1 rs28357094 and subclinical markers of carotid atherosclerosis at the time of recruitment. Moreover, we did not find any statistically significant effect of either rs4754 or rs28357094 on subclinical markers of carotid atherosclerosis progression (CIMT progression, change in total plaque thickness, change in the number of sites with plaques). As shown by the multiple linear regression analysis, genotypes of either rs4754 or rs28357094 did not have a statistically significant effect on the progression of subclinical markers of carotid atherosclerosis (CIMT progression, change in total plaque thickness, change in the number of sites with plaques) after the adjustment for confounding variables. CONCLUSIONS: We demonstrated an important effect of the SPP1 rs4754 on subclinical markers of carotid atherosclerosis in subjects with T2DM; however, as demonstrated by the multiple linear regression analysis, neither rs4754 nor rs28357094 had an important impact on the progression of subclinical markers of carotid atherosclerosis in subjects with T2DM.