Insertion/Deletion Polymorphism of Angiotensin-Converting Enzyme as a Risk Factor for Chronic Allograft Nephropathy

Angiotensin-converting enzyme (ACE) inhibitor therapy is widely used to treat chronicallograft nephropathy (CAN), which suggests a possible role of the renin-angiotensin system inthe pathologic mechanism of the disease. The objective of this study was to investigate thepossible link between CAN and ACE. The ACE insertion/deletion polymorphism and theamount and activity of ACE were determined in cadaver kidney recipients with CAN (n = 38)or normal renal function (n = 34). The DD genotype was observed significantly morefrequently in the CAN group compared with the group with normal renal function. Moreover,the DD genotype was associated with a higher serum ACE concentration and greater serumACE activity, compared with II genotype homozygotes. The insertion/deletion polymorphismof ACE affects ACE expression and activity in serum, and, therefore, may have an importantrole in the pathogenesis of CAN. These findings suggest that determination of the ACEgenotype may be useful in identifying patients at high risk. In particular, the DD genotype maybe considered an indication for ACE inhibitor therap

Human paraoxonase-1 activity in childhood obesity and its relation to leptin and adiponectin levels

Childhood obesity is a predisposing factor for adult cardiovascular diseases. Human serum paraoxonase (PON1) may protect against atherosclerosis by hydrolyzing lipid peroxides in oxidized LDL. Alterations and potential correlations of PON1 activities, leptin and adiponectin levels in childhood obesity were studied. We measured PON1 paraoxonase and arylesterase activities, anthropometric parameters, leptin and adiponectin levels in 59 white, obese (obese group-OB: BMI corrected for age: 95.1?3.5 percentile, age: 11.9?1.6 years) and 51 normal-weight children (control group-C: BMI corrected for age: 64.1?8.4 percentile, age: 12.0?3.9 years). Obese children had significantly lower PON1 paraoxonase (OB:84.80(64.33/144.74)U/l vs. C:99.42(83.33/152.05)U/l; p<0.05) and arylesterase activities (OB:94.40(82.20/108.70)U/l vs. C:115.20(93.70/126.00)U/l; p<0.01), higher leptin (OB:37.05(24.33/53.87)ng/ml vs. C:4.62(2.52/17.6)ng/ml; p<0.0001) and lower adiponectin levels (OB:7.56(5.69/12.06)?g/ml vs. C:11.51(8.84/14.49)?g/ml; p<0.001) compared to the normal-weight group. PON1 arylesterase activity showed inverse univariate correlation with leptin (r=-0.29; p<0.05) and positive correlation with adiponectin levels (r=0.39; p<0.01). In multiple regression analysis adiponectin was strongly associated with PON1 arylesterase activity in obese children (?=0.45, p<0.02). Our results emphasize the importance of the investigated metabolic alterations which may have further effects on cardiovascular morbidity and mortality in later adulthood. Altered levels of leptin, adiponectin and PON1 activities may be useful markers beside the general risk factors in childhood obesit