Apolipoprotein E polymorphism, paraoxonase-1 activity and coronary artery disease: is there a link

The association of ApoE allele frequencies with coronary artery disease [CAD] remains unknown in developing countries. Paraoxonase 1 [PON1] is an enzyme that is associated with high density lipoprotein [HDL] and hydrolyzes oxidized lipids in oxidized low density lipoprotein [LDL] and thus protects against the development of atherosclerosis. In this study the association of apoE polymorphism and PON1 with premature CAD was determined. The frequency of apo E alleles and the activity of the PON1 among 162 patients with early and late onset CAD was examined. The mean age in the early and late-onset groups were 44.9 ' 4.9 and 71.7'2.5 years respectively. Patients with early-onset CAD had significantly lower serum levels of HDL-C and higher LDL-C/HDL-C ratio than the late-onset group. There was no difference in serum levels of triglyceride, total cholesterol and LDL-C between the two groups. The e2 allele was significantly higher in the late-onset group. 35.0% of early-onset and 17.5% of late-onset group had low level of PON1. 86% of the early-onset CAD and all of the late-onset CAD patients with e3/ e4 genotype, had low or moderate level of PON1 activity. We found a positive association between PON1 activity, HDL level and the onset of CAD. Our study suggests that there are modest associations between CAD and apo E alleles and that the lower activity of PON1 in the presence of lower apo E level may increase the susceptibility to early-onset CAD

Serum cystatin C as a new marker of glomerular filtration rate [GFR]

Cystatin C is a 13 KD basic protein that is a member of the cystatin super-family of cysteine protease inhibitors. The cystatin C gene seems to be a house keeping gene, which is compatible with a stable production rate of cystatin C by most cells. This protein is freely filtered through the glomerulus and almost completely reabsorbed and catabolized by proximal tubular cells. Because of these characteristics cystatin C is assumed to be a better marker of glomerular filtration rate than other markers. 115 new cases of renal disease aged between 14 and 88 years and 121 healthy subjects, aged between 11 and 78 years were studied. In all of the subjects serum cystatin C and creatinine were determined and creatinine clearance was determined only in patients. Cystatin C was determined by a particle-enhanced turbidimetric assay and creatinine was measured by Jaffe's method. In addition, to assess the diagnostic efficiency of serum cystatin C in comparison to that of serum creatinine and creatinine clearance in predicting changes in GFR, we performed Tc99m - DTPA clearance on 53 subjects including controls and patients. A linear relationship was found between Tc99m - DTPA clearance and Y serum cystatin C [r= 0.712, p-value <0.001], 1/serum creatinine [r= 0.709, p-value< 0.001] and creatinine clearance [r= 0.777, p- value <0.001]. Diagnostic accuracy in the identification of reduced GFR measured as area under the receiver-operating characteristic plot was 0.878 +/- 050 [Mean +/- SE] for Scystatin C, 0.866 +/- 0.051 for creatinine and 0.866 +/- 0.051 for creatinine clearance. The serum cystatin C reference values [mean +/- 1.96 SD] determined was 0.83 -0.88 mg/L. A cutoff cystatin C concentration of 0.82 mg/L had 92% sensitivity and 79% specificity for detecting abnormal GFR. There was no significant correlation between cystatin C and age [p- value <0.219] and weight [p- value <0.193]. This study demonstrates that serum cystatin C has an increased diagnostic accuracy for reduced GFR when compared with serum creatinine and creatinine clearance. Hence, cystatin C seems to be an alternative for the estimation of GFR