Single-nucleotide polymorphism analysis of the multidrug resistance protein 3 gene for the detection of clinical progression in Japanese patients with primary biliary cirrhosis

Abstract

Primary biliary cirrhosis (PBC) is a multifactorial disease in which genetic factors rather than environmental factors may predominantly contribute to the pathogenesis. In order to identify the genetic determinants of the disease severity and progression of PBC, we examined an association of seven tag single-nucleotide polymorphisms (SNPs) in the multidrug resistance protein 3 (MDR3/ABCB4) gene in 148 Japanese PBC patients and 150 age-and sex-matched healthy control subjects. SNPs were detected via polymerase chain reaction (PCR) restriction fragment length polymorphism and PCR direct DNA sequencing methods. Subsequently, haplotypes were constructed from three tag SNPs (rs31658, rs31672, and rs1149222) that were significantly associated with progression of PBC. Logistic regression analyses revealed that a Hap 2 haplotype and its homozygous diplotype, Hap 2/Hap 2, in MDR3 were closely associated with the susceptibility to jaundice-type progression of PBC [P ‫؍‬ 0.004, odds ratio (

The state of cholesterol metabolism in the liver of patients with primary biliary cirrhosis: the role of MDR3 expression

“…In other words, GGT and IgM levels appear to represent PBC disease activity. Our results support recent reports using singlenucleotide polymorphism analysis, which showed that MDR3 haplotypes and diplotypes are associated with the progression of PBC [21,22]. In this study, the patients, in whom GGT and IgM levels were already elevated (Table 2), were in the early stages and without any medication for PBC.…”

Genetic polymorphisms in CTLA4 and SLC4A2 are differentially associated with the pathogenesis of primary biliary cirrhosis in Japanese patients

“…CTLA4 and SLC4A2 SNPs were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and TaqMan SNP Genotyping assays as previously described [6,10]. All primers and probes for the TaqMan SNP Genotyping assays were purchased from Applied Biosystems (Foster City, CA, USA).…”

“…Many candidate gene association studies have been performed and several single nucleotide polymorphisms (SNPs) have been associated with PBC, including human leukocyte antigen (HLA), cytotoxic T-lymphocyte antigen 4 (CTLA4), solute carrier family 4 anion exchanger, member 2 (SLC4A2), tumor necrosis factor, and programmed cell death 1 and multidrug resistance protein 3 [2][3][4][5][6][7][8][9][10][11][12][13]. In addition to these genes, recent genome-wide association studies have revealed that IL12A, IL12RB2, IRF5-TNPO3, 17q12-21, and MMEL1 loci were associated with PBC susceptibility in Caucasians [14][15][16].…”

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

“…Among the non-HLA loci, strong association signals with PBC were found for SNPs in IL12A, IL12RB, STAT4, CTLA4, DEN-ND1B, CD80, IL7R, CXCR5, TNFRSF1A, CLEC16A and NFKB1 [11]. Furthermore, HLA [37] and non-HLA gene polymorphisms (MDR3, A2BP1) [38,39] have also been implicated with the onset or progression of PBC. Endothelin polymorphisms have been investigated in cardiovascular diseases and hypertension, but there are also a few reports in other autoimmune diseases such as vitiligo [40], psoriasis [41], scleroderma [42], primary Raynaud [43].…”