[IL1/IL1 Ra, DTLA-4 and Apol/Fas genes polymorphisms and susceptibility to IgA nephropathy in Tunisian patients]

ABSTRACT

The IgA nephropathy [IgA-N] is considered the most common form of primary glomerulonephritis and its pathogenic mechanisms are very complex. The study of several genes which encode for immunoregulator molecules in inflammatory and immunological responses during the disease, allowed to describe some number of polymorphisms would be involved in the molecular expression, the road marking, the synthesis and/or the binding to the receptors. So an abnormality of the molecular function associated with its polymorphism would be suggested in the genetic predisposition to the disease. To determine interleukin 1 [IL1], interleukin1 receptor antagonist [IL1 Ra], CTLA-4 and Apol/Fas genespolymorphisms frequencies in IgA-N in order to estimate the impact of these polymorphisms in the disease susceptibility. The polymorphism of a single nucleotide [SNP] at [-889] IL1 alpha of 21 IgA-N patients and 100 healthy blood donors, as controls, was studied by PCRSSP. The SNPs of the IL1 beta [+3954], CTLA-4 [+49] and l'Apol/Fas were analyzed by PCR RFLP and finally the polymorphism of the IL1 Ra gene was determined by a PCR VNTR [variable number tandem repeat]. Investigation of IL1 alpha/beta and Apol/ Fas polymorphisms showed no differences in genotypes and allelesfrequencies between IgA-N patients and controls. However, genotype AA of CTLA-4 exon 1 [+49] was significantly higher in patients [47.62%] than in controls [9,1%] p<0.001. Nevertheless, the clinical histological and biological characteristics of IgA-N were similar in AA CTLA-4 genotype patients compared to AG or GG genotype patients. We fund also, a significant increased frequency of 1/1 IL1 Ra genotype in IgA-N patients [95,24%] compared to controls [54%] [p<0,001] [p<0,001]. We conclude that the susceptibility to IgA-N seems to be associated with the presence of CTLA-4 AA and iL1 Ra 1/1 genotypes in Tunisian population. However, the lack of association between IL1 alpha/ beta and Apol/fas genes polymorphisms should be further investigated by large population based studies