Background: The very high cardiovascular (CV) mortality and morbidity rates in hemodialysis (HD) patients are greatly related to atherosclerosis. CCN2 (connective tissue growth factor/CTGF) is a profibrotic factor that is secreted by endothelial cells, involved in atherogenesis, promoting fibroblast proliferation and matrix production. CCN2 protein is significantly increased in complicated fibrous plaques and enhances monocyte migration into atherosclerotic lesions. The aim of this study was to investigate a possible association between CCN2 gene polymorphism and CV morbidity and mortality in HD patients. Methods: 98 HD patients, followed for 24 months, were genotyped for the common polymorphism on the CCN2 gene (G-945C). HD patient characteristics were: age 64 ± 13 years, males 64%, diabetes 24%, hypertension 62%, smokers 38%, dyslipidemia 28%, all undergoing standard HD three times weekly. Results: All-cause mortality was not associated with CCN2 polymorphism (G-945C). In contrast, however, the GG genotype was strongly associated with CV mortality: OR 13 (1.49–155), p = 0.0048. Interestingly, the GG genotype was also greatly associated with the serious CV events of stroke and myocardial infarction in surviving HD patients: OR 13.3 (2.5–87.08), p = 0.0001. Conclusions: We demonstrate for the first time that CCN2 gene polymorphism is a prognostic risk factor for CV morbidity and mortality in HD patients. These data may have important implications for better understanding the link between accelerated atherosclerosis and increased mortality in HD population.

Gilbert's syndrome is characterized by unconjugated nonhemolytic hyperbilirubinemia and mild intermittent jaundice. Its molecular basis results in a TA repeat insertion (TA7) in the TATA-box of the UDP-glucoronosyltransferase gene promoter (UGT1A). In 1999 we introduced the Gilbert's syndrome genetic test to analyze the relationship between the genetic variant TA7 and the bilirubin concentration in a sample of 98 subjects from all Italian regions. From 1999 to 2008 we analyzed the polymorphism's influence on bilirubin metabolism in a larger population (500 subjects) and evaluated the appropriateness of the genetic analysis requests in the Gilbert's syndrome diagnostic procedure by comparing results with those of the previous study. The TA7 homozygous distribution was statistically different between the two groups (16.3% in the first vs. 54,0% in the second one; P=0.00001). The bilirubin concentrations were higher in TA7 homozygous subjects when compared with heterozygous and normal ones (TA7/TA7, 1.47 +/- 0.67 mg/dL; TA6/TA6, 0,68 +/- 0,29 mg/dL; P=0.009).