Wei Wang

Background: The aim of the present cross-sectional study was to assess possible associations between osteopontin (OPN), and thrombin-cleaved (N-half) OPN, and nephropathy and coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). Methods: Plasma levels of OPN, N-half OPN, and high-sensitivity C-reactive protein (hsCRP) were determined in 301 diabetic patients with (n = 226) or without (n = 75) angiographically documented CAD (luminal diameter narrowing >50%), as well as in 75 non-diabetic controls with normal angiography. The estimated glomerular filtration rate (eGFR) was calculated in all patients. Results: Plasma levels of OPN and hsCRP were significantly higher in patients with T2DM compared with controls. In addition, there was a higher occurrence of moderate renal insufficiency and lower eGFR in patients with T2DM (all P < 0.01). T2DM patients in whom OPN levels were greater than the median value had higher serum creatinine levels, a greater prevalence of mild or moderate renal insufficiency, a higher incidence of CAD, and lower eGFR (all P < 0.05) than T2DM patients in whom OPN levels were the same as or lower than the median value. However, there were no differences in these parameters when patients were stratified according to plasma N-half OPN levels. Furthermore, there was a significant correlation between OPN, but not N-half OPN, and the severity of nephropathy and CAD in diabetes. After adjustment for potential confounders and treatments, multiple linear regression analysis demonstrated an independent association between OPN, but not N-half OPN, and eGFR. Multivariate logistic regression revealed that higher OPN levels conferred a fourfold greater risk of renal insufficiency and CAD in patients with T2DM. Conclusions: The results of the present study demonstrate that there is an independent association between plasma levels of OPN, but not N-half OPN, and the presence and severity of nephropathy and CAD in diabetes.

Background: We sought to explore the association of variant rs1333049 on chromosome 9p21.3 with coronary artery disease (CAD) and angiographic plaque progression in non-diabetic and type 2 diabetic patients. Methods: Genotyping and quantitative coronary angiography (QCA) were performed in 2046 Chinese Han patients (1012 diabetic cases) undergoing coronary angiography; 430 of them received repeat angiographic studies at 1-year follow-up. Results: CC genotype at rs1333049 on chromosome 9p21.3 was associated with CAD (unadjusted OR 1.524, p = 0.001 and adjusted OR 1.859, p = 0.005, respectively). However, CC genotype had no magnified association with CAD in diabetic patients (OR 1.275, p = 0.150) compared with non-diabetic counterparts (OR 1.446, p = 0.020) after adjusting for conventional risk factors. During angiographic follow-up, non-diabetic patients (n = 280) had significant decrease in minimal lumen diameter and increase in percent diameter stenosis among the three genotypes (p = 0.005 and p = 0.038, respectively), demonstrating that CC or GC genotype carriers had a more severe plaque progression than GG genotype carriers. In patients with type 2 diabetes (n = 150), although plaque progression was more severe than that in non-diabetic counterparts, no relations existed between plaque progression and genotypes. Rs1333049 was an independent determinant of plaque progression for non-diabetic (OR 3.468, p = 0.004 and OR 4.339, p = 0.002 for GC and CC genotype, respectively) but not for diabetic patients (OR 0.529, p = 0.077 and 0R 0.878, p = 0.644 for GC and CC genotype, respectively). Conclusions: This study demonstrates a significant association of homozygous CC genotype of rs1333049 on chromosome 9p21.3 with CAD in Chinese Han population. Rs1333049 polymorphism is an independent determinant for coronary plaque progression in non-diabetic but not in type 2 diabetic patients.