Polymorphisms of genes related to endothelial cells are associated with primary biliary cirrhosis patients of Cretan origin

Abstract Background Primary biliary cirrhosis (PBC) is an organ specific autoimmune disease of still unidentified genetic etiology. We have shown that endothelins (ETs), produced by the liver endothelial cells are increased in PBC and may play a major pathogenetic role. Aims To study gene polymorphisms related to the endothelial cells ( eNOS , EDN-1 genes) and, to investigate whether the previously reported association of CTLA4 gene polymorphisms is replicated in a genetically homogeneous Greek population. Patients and methods Genomic DNA was extracted from 100 PBC patients (83 females, 93% AMA+, 74/100 Ludwig stage I–II) and 158 healthy controls. eNOS , CTLA4 and ET1 polymorphisms were determined by PCR–RFLPs analysis. Results Both eNOS intron4 VNTR and eNOS exon7 G894T SNP were significantly associated with increased risk in PBC. EDN-11 rs2071942 “A” and rs5370 “T” alleles appeared a tendency for association with disease progression. No association was found between PBC and the CTLA4 SNPs analyzed. Conclusions We demonstrated that eNOS , a gene related to the liver endothelium function is associated with PBC. Contrarily, the important in adaptive immunity gene CTLA4 was not associated with the disease in the homogeneous population analyzed. These results are compatible partially with our previous hypothesis that defects of the liver endothelial system, leading to endothelin overproduction, may be a fundamental early pathogenetic mechanism in PBC.