ETIOLOGY OF BALKAN ENDEMIC NEPHROPATHY - A MULTIFACTORIAL DISEASE

Balkan endemic nephropathy (BEN) is of great clinical importance in th e restricted areas of Bulgaria, Rumania, Croatia, Serbia, Bosnia and H erzegovina. So far, studies on the etiological factors for BEN have no t discovered any single environmental causative agent of this puzzling disease. These data reject the possibility of a purely environmental causation of BEN. The pattern of BEN transmission in the risk families is not typical for single gene disorders. Extensive epidemiological a nd genetic studies disclose characteristics of multifactorial (polygen ic) inheritance of BEN. The evidences of 'familial tendency', variatio n of the risk for BEN depending on the number of sick parents and the degree of relatedness; the development of BEN in individuals from at-r isk families who were born in non-endemic areas; the data that disease is not found in the gypsy population and the expressions of 3q25 cyto genetic marker suggest that the genetic factors play an important role as causative factors in BEN development. The possible impact of envir onmental triggers on individuals genetically predisposed to BEN could be supposed by the following data: the cytogenetic results of the incr eased frequency of folate sensitive Era sites, spontaneous or radiatio n-induced aberrations in several bands in BEN patients, the data from the detailed analysis of breaks in BEN patients and controls that gene rate structural chromosome aberrations; the occurrence of BEN in immig rants. Genetical epidemiological approaches to etiology and prevention of BEN are proposed. The predisposing genes for BEN could be genes lo calized in a region between 3q25-3q26; transforming growth factor-beta (TGF-beta), genetic heterogeneity of xenobiotic-metabolizing enzymes; defects in the host's immune system. The predisposing genes for BEN p atients with urinary tract tumors could be germline mutations in tumor suppressor genes and acquired somatic mutations in oncogenes.