الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Renal stones are one of the most common disorders of the urinary tract. Calcium nephrolithiasis is the most common type of renal stones representing about
70-80%. It may be considered a complex disease having multiple pathogenetic mechanisms.
Both genetic and environmental factors may increase susceptibility to calcium stones. The pattern of hereditary transmission has not been ascertained yet, but it is likely that multiple genes having a small causal effect may contribute to increase susceptibility to stones. In some studies, heritability of calcium stones was calculated around 50%.
The calcium sensing receptor (CaSR) represents the molecular mechanism by which parathyroid cells detect changes in blood ionized calcium concentration and modulate parathyroid hormone (PTH) secretion to maintain serum calcium levels within a narrow physiological range.
In the kidney, CaSR prevents the reabsorption of divalent cations in the cortical thick ascending limb of Henle’s loop and triggers the inhibitory actions of hypercalcemia on the urinary-concentrating mechanism, and because alteration in calcium homeostasis is considered the most important risk factor for calcium nephrolithiasis, mutations in the CaSR gene are candidates for explaining calcium nephrolithiasis pathogenesis.
So, recent studies have attempted to understand the genetic effects of CaSR gene SNPs on increased susceptibility to calcium stones. Multiple SNPs were detected to be associated with nephrolithiasis as rs7652589, rs1501899, A986S (rs1801725), R990G (rs1042636), and Q1011E (rs1801726). In addition, a CaSR genetic polymorphism (rs17251221) is strongly associated with disturbance in serum calcium concentration in individuals of European and Indian-Asian descent.
So, the present study aimed to evaluate the relation between CaSR gene polymorphism (rs17251221) and the development of calcium nephrolithiasis in the Egyptian population. This study included forty selected Egyptian patients admitted to Urosurgery Department at Alexandria Main University Hospital, suffering from calcium nephrolithiasis which was confirmed by radiological investigations and chemical stone analysis, whose age ranged from 29 to 68 years with a mean of 47 years, including 65% males and 35% females. Patients with chronic urinary tract infection, renal failure, chronic diarrhea, gout, renal tubular acidosis, diabetes mellitus, hyperparathyroidism, malignancy or regular intake of diuretics, vitamin D, or calcium supplements were excluded to the relation between these diseases and the development of calcium nephrolithiasis. Also, forty healthy individuals, whose age ranged from 21 to 77 years with a mean of 44 years, including 47.5% males and 52.5% females with no history or family history of calcium renal stones were included as a control group.
Three milliliters of whole blood were collected from every participant by aseptic venipuncture in a plain tube, then the serum was used for assessment of creatinine, calcium, phosphorus and uric acid. Another 2 mL were drawn into EDTA tubes. The DNA in each sample was extracted using PureLink® Genomic DNA Mini Kit. Genotype of patients and controls was detected using real time PCR with dual fluorescence and allelic discrimination assay, readymade genotyping reagents (Applied Biosystems, USA).