REAL-TIME POLYMERASE CHAIN REACTION FOR GENOTYPING OF THE TRANSFORMING GROW FACTOR β1 POLYMORPHISM Thr263Ile IN PATIENTS WITH BALKAN ENDEMIC NEPHROPATHY AND IN A HEALTHY BULGARIAN POPULATION
Atanasova S1, von Ahsen N2, Dimitrov Tz3, Armstrong V2, Oellerich M2, Toncheva D1,*
*Corresponding Author: Professor Draga Toncheva, Ph.D., Department of Medical Genetics, Medical University Sofia, 2 Zdrave str., Sophia, Bulgaria; Tel/Fax: +359-2-9520-357; E-mail: draga@spnet.net
page: 37

INTRODUCTION

A number of kidney diseases, and their progression to the end-stage renal failure, are characterized histolog­ically by the accumulation of extracellular matrix in the renal interstitium and progressive tubular atrophy. Several studies indicate that the hypertrophy of mesengial and tubular cells is related with induction of TGFb1 [1,2]. Transforming growth factor b is a multi-functional cyto­kine that plays a key role in cellular growth, proliferation and differentiation. TGFb1 regulates the formation of the extracellular matrix. It was generally considered that TGFb1 have a pro-fibrotic effect by increasing collagen production and decreasing proteolytic enzyme-collagenase [2]. It was accepted that local production of TGFb1, by intrinsic renal cells or by macrophages invading the kid­ney, is a key mediator for renal fibrosis [3].

In vitro production of TGFb1 correlates with the gene variant at codon 25. The polymorphism G915C in this codon (arginine to proline) is associated with inter-indi­vidual variation in levels of TGFb1 production. Individu­als homozygous for the arginine/arginine variant at codon 25 showed enhanced production of TGFb1 in the stimu­lated lymphocytes, compared to the lymphocytes of het­erozygous arginine/proline individuals [4]. It was shown that homozygosity for arginine at codon 25 is associated with fibrotic lung pathology and fibrosis in the graft after lung transplantation [5]. A second polymorphism is lo­cated at codon 10 (leucine to proline), and together with homozygosity for the codon 25 arginine. is a marker for enhanced fibroses after lung transplantation [5].


The Thr263Ile polymorphism is result of CT substi­tution in the part of the propeptide that is cleaved from the active part of the protein. It was supposed that the codon 263 polymorphism is involved in the activation process of the TGFb1 protein [6].

BEN is a chronic renal disease, with slow progression leading to the end-stage nephropathy. At the end-stage, the disease shows damage in tubular function, severe alter­ations in the external renal cortex and bilaterally shrunken kidneys [7]. In the kidneys of BEN patients, interstitial (accumulation of proteins, higher numbers of fibroblasts) and vascular lesions (large numbers of collagen fibers of various dimensions), were observed [8]. A possible contri­bution of TGFb1 to BEN pathogenesis was supposed [9]. The aim of this study was to establish the frequency of Thr263Ile in TGFb1 in BEN patients and healthy individ­uals, in order to evaluate the role of TGFb1 for disease initiation and progression.




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