BALKAN ENDEMIC NEPHROPATHY RISK ASSOCIATES TO THE HS1.2 IG ENHANCER POLYMORPHISM

Balkan Endemic Nephropathy (BEN) is a kidney degenerative disease with a high incidence in the valleys of the Danube and tributary rivers. Many evidences describe it as a multifactorial disease. Environmental as well immuno-inflammatory and genetic cofactors have been suggested to trigger the onset of the disease. Recently, high levels of C-reactive protein were demonstrated in BEN patients. We performed this study to evaluate the possible correlation of BEN with the polymorphism of the Ig heavy chain 3’Regulatory Region enhancer hs1.2 that is related to changes of consensus for trans activators binding within the DNA sequence and probably consequently autoimmune and inflammatory diseases. Therefore, we studied three cohorts: 1) 111 control subjects, 2) 95 BEN patients in dialysis therapy and 3) 133 components of a large family “J” the same geographical area. The allelic frequencies of hs1.2 of BEN patients and family “J” components had the similar decrease frequency of allele *1 and increase of allele *2 respect to the controls. This trend suggests the association of allele *1 as a protective and allele *2 as a risk component for the disease. The presence of a consensus sequence for NF-kb in the allele *2 may link the polymorphism to the inflammatory activity of BEN. This study supports the presence of an inflammatory pathway in BEN through the involvement of polymorphic enhancer hs1.2 influencing differently binding complexes and consequently the 3D structure of 3’ Regulatory Region of IgH. Our work is the first study that clearly links BEN to a gene involved in the regulation of immune response.