Association of chitotriosidase enzyme activity and genotype with the risk of nephropathy in type 2 diabetes.

OBJECTIVE: The immune-inflammatory system has been implicated in the pathogenesis of diabetic nephropathy; however, many of the mechanisms involved remain unclear. Chitotriosidase enzyme is an active human chitinase and a major protein product of activated macrophages. Although playing an important role in innate and acquired immunity, chitotriosidase involvement in the development of diabetic nephropathy is unknown. DESIGN AND METHODS: Chitotriosidase enzyme activity and the presence of the functional 24-bp duplication mutation of the chitotriosidase gene (CHIT1) were assessed in 262 Egyptian type 2 diabetic patients with and without nephropathy and 90 non-diabetic controls. In diabetic patients, multiple linear regression models were adapted to assess the association of chitotriosidase activity with two important measures of renal disease progression: urinary albumin/creatinine ratio and eGFR, while the association of the CHIT1 genotype with the incidence of nephropathy was evaluated by multiple logistic regression. RESULTS: In diabetic patients, chitotriosidase enzyme activity showed a statistically significant elevation as compared to controls and correlated positively with the progression of nephropathy. A significant association of chitotriosidase activity with both urinary albumin/creatinine ratio and eGFR was detected after adjusting for age, gender, duration of diabetes, body mass index, hypertension status, total cholesterol, triglycerides and HbA1c levels, P<0.001. We also identified a protective association between the CHIT1 mutated genotype and diabetic nephropathy after adjusting for the same confounders (odds ratio: 0.517, 95% CI: 0.289-0.924, P=0.026). CONCLUSIONS: This study demonstrates for the first time that the immunomodulatory effects of chitotriosidase enzyme could be implicated in the development of nephropathy in type 2 diabetes.

Transforming growth factor-ß1 gene expression in hepatocellular carcinoma: a preliminary report.

BACKGROUND AND STUDY AIMS: The transforming growth factor (TGF)-ß signalling pathway plays a dual role in hepatocarcinogenesis. It has been recognised for its role as a tumour suppressor as well as a tumour promoter depending on the cellular context. The aim of this study was to investigate the clinical significance of serum TGF-ß1 level and TGF-ß1 messenger RNA (mRNA) in the peripheral blood of liver cirrhosis and hepatocellular carcinoma (HCC) patients as noninvasive biomarkers in diagnosing HCC. PATIENTS AND METHODS: Twenty patients were allocated to each of the liver cirrhosis and HCC groups, in addition to 20 healthy volunteers. TGF-ß1 gene expression in peripheral blood was quantitated using real-time polymerase chain reaction (PCR), while serum TGF-ß1 was analysed using enzyme-linked immunosorbent assay (ELISA). RESULTS: TGF-ß1 gene expression was significantly lower in HCC patients (median 0.401 (0.241-0.699) fold change) than in liver cirrhosis patients (median 0.595 (0.464-0.816)) (p=0.042) and normal controls (median 1.00 (0.706-1.426) fold change) (p=0.001). TGF-ß1 gene expression showed significant positive correlation with serum TGF-ß1 (r=0.272, p=0.036) and significant negative correlation with alpha-fetoprotein (AFP) (r=-0.528, p=0.001). Receiver operating characteristic (ROC) analysis was conducted for TGF-ß1 gene expression in comparison with AFP. The area under the curve for TGF-ß1 gene expression was 0.688 (95% CI=0.517-0.858) (p=0.042) and AFP was 0.869 (95% CI=0.761-0.976) (p=0.001). The sensitivity and specificity of TGF-ß1 gene expression were 65% and 75%, respectively, at a cutoff value of 0.462 fold change. CONCLUSION: TGF-ß1 gene expression in the peripheral blood may be used as a molecular marker for the diagnosis of HCC. Additional studies on a large-scale population are necessary to gain greater insight into the impact of TGF-ß1 gene expression in the pathogenesis of HCC.