Paraoxonase gene polymorphism and serum paraoxonase activity: relationship with type I diabetes and nephropathy

Human serum paraoxonase-I [PON1] is physically associated with high density lippprotein [HDL] and has been implicated in the prevention of LDL lipid peroxidation. PON1 gene displays several polymorphisms that influence both its level of expression and its catalytic activity. The goal of this study was to examine the association between paraoxonase-1 [PON1] activity and gene polymorphism and the micro-vascular complications in children and adolescence suffering from type 1 DM [TIDM]. Case-control study. One study centre at a University hospital. Thirty eight patients, with type 1 diabetes [n=38], 13 patients presenting with diabetic nephropathy [mean age 18.76 +/- 5.59 years. 8 males and 5 females] and 25 without diabetic nephropathy [mean age 14.48 +/- 3.69 years. 14 males and 11 females] and 16 healthy controls [mean age 12.38 +/- 8.25 years, 10 males and 6 females]. The allele variants of PON1 gene polymorphisms in the PON1 coding region Q192R and L55M have been identified by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Serum PON1 enzyme activity was measured spectrophotometrically. Serum PON1 activity was significantly decreased in complicated diabetics when compared to both non-complicated patients and the control persons [103.33 +/- 35.46 nmol/ml/min, 462.57 +/- 200.69 nmol/ml/min and 1132 +/- 317.61 nmol/ml/min respectively]. As regards PON1 Q192R polymorphism, the R allele was more frequent in complicated diabetics versus both non-complicated diabetics and controls [p=0.0113 and p=0.001 respectively]. PON1 192QR genotype is a risk factor for developing type 1 diabetes OR=7.8; 95% CI [1.12-65.7] with p=0.043. PON1 192QR genotype and 192R allele are risk factors for developing micro-vascular complications with OR =6.40 and 4.00; 95% CI [1.44.28.29] and [1.15-13.87] with p=0.01 and 0.023 respectively. In PON1 L55M polymorphism, non significant differences in the genotype or allele frequency were found between T TIDM, both complicated and non-complicated diabetics and control persons. The association of PON1 Q192R polymorphisms, lower PON1 activity and poorer diabetic control found in patients with diabetic nephropathy further support an idea of genetic factors contributing to development of vascular complications in diabetes

Vitamin D receptor [VDR] gene polymorphism and risk of osteoporosis in Egyptian post menopausal women

Identifying people at risk of osteoporosis is very important, as prevention is possible. Because genetic factors were shown to have a great influence on osteoporosis susceptibility, their study may be of great help in targeting high-risk individuals. In this work, we studied the association between VDR gene polymorphism and bone mineral density in postmenopausal Egyptian females. 45 Egyptian postmenopausal women [57 +/- 4.6 years] were studied. Bone mineral density was measured at the lumbar spines, the hip, and the lower radius using dual energy X-ray absorptiometry. Ten of the studied patients [22%] had osteoporosis [T or z scores < -2.5]; 21 [47%] had osteopenia [T or z scores -1 to -2.5]; and 14[31%] were normal [T or z scores > -1]. Restriction fragment length polymorphisms in the VDR gene were assessed by PCR amplification and digestion with restriction enzymes FokI, BsmI, ApaI, and TaqI recognizing polymorphic sites in these four VDR gene loci. The BsmI Bb genotype distribution was significantly higher in the normal postmenopausal women [42.9%] than osteopenic women [4.8%] [p value < 0.002]. The TaqI [T] allele was significantly higher in the normal group [68.0%] than the osteopenic group [45.0%] and TaqI [t] which was significantly higher in the osteopenic group [55.0%] than the normal group [32.0%] [p=0.031 for both], otherwise, there was no significant difference in the distribution of other VDR genotypes in relation to bone density measurement. The higher distribution of the VDR BsmI Bb and TaqI T genotype in the normal postmenopausal than osteopenic women may reflect a protective role, on the other hand, TaqI t allele may be associated with lower bone mineral density in postmenopausal Egyptian females