Investigation of Common Variations of ABCB4, ATP8B1 and ABCB11 Genes in Patients with Progressive Familial Intrahepatic Cholestasis

Background Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of hepatic disorders that can progress rapidly, leading to cirrhosis and death due to liver failure. Mutations and variations in three genes, including ATP8B1, ABCB11, and ABCB4, have been reported to be the main genetic cause of three subtypes of this disorder including PFIC1, PFIC2, and PFIC3, respectively. Objectives Therefore, the aim of this study was to investigate more common mutations and variations associated with PFIC considering clinical and Para-clinical features of the disease. Methods Thirty-five unrelated patients with PFIC from the south of Iran were selected randomly among all PFIC patients referring to Namazi hospital, affiliated to Shiraz University of Medical Sciences. Genomic DNA was extracted from the peripheral blood lymphocytes. Sequences related to these variations were then amplified by PCR in the 35 cholestasis patients and analyzed by Sanger® sequencing. Results The results showed that there was no variation in interest exon of ABCB4. Moreover, in ATP8B1, there was no prevalent mutation and only an unknown significant variation (c.*1101 + 366G > A) was found. However, in the ABCB11 gene, different variations were found including c.1434 + 174G > A, c.1434 + 70C > T, c.1331T > C (p.Val444Ala, a common variant proposed to be associated with cholestasis), c.1309-93G > A, c.1309-165C > T. Also, 11 and 13 cases showed heterozygote and homozygote, respectively, for V444A variation of the ABCB11 gene. Conclusions The allele frequency of V444A in this study was 52.8%. This variation has been previously implicated with higher frequencies in ICP and DIC than normal subjects, suggesting that this variation may become disease-relevant in certain conditions.