Association between ABCB1 (MDR1) Gene 3435 C>T Polymorphism and Colchicine Unresponsiveness of FMF Patients

Abstract

The multidrug resistance gene-1 (MDR1, adenosine triphosphate-binding cassette transporter: ABCB1, P-glycoprotein) encodes membrane proteins that play a crucial role in protecting cells from xenobiotics, chemicals, and drugs. The TT genotype of 3435 codon in exon 26 of MDR1 gene causes overexpression of gene activity and effluxes many chemically diverse compounds across the plasma membrane. We studied the association between C3435T polymorphisms (single nucleotide polymorphism) of MDR1 gene and colchicine-resistant familial Mediterranean fever (FMF) patients. Total genomic DNA samples from 52 FMF patients of colchicine unresponsiveness were used for FMF (MEFV) and MDR1 genes profile analyses. Target genes were genotyped by multiplex PCR-based reverse-hybridization Strip Assay method. The preliminary current results showed increased T allele frequency (0.596) in colchicine unresponsiveness of FMF patients. The distributions of the CC, CT, and TT genotypes in colchicine nonresponder FMF patients were 17%, 46%, and 37%, respectively. Our results indicate that C3435T polymorphism in exon 26 of MDR1 gene is associated with colchicine resistance in nonresponder FMF patients during the common therapy protocol.

Colchicine—Update on mechanisms of action and therapeutic uses

“…The P-gp/MDR1 gene is highly polymorphic with more than 70 single nucleotide polymorphisms (SNPs) defined to date [50]. Polymorphisms of the MDR1 gene have been shown to change both the expression level and function of P-gp, and might be associated with colchicine resistance in some small sample studies in FMF [51][52][53] and BD [54]; but not in all studies [55][56]. In general, further studies with a larger sample size are needed to better understand the role of MDR1 gene polymorphisms in the colchicine response of patients with different conditions.…”

Association Between ABCB1 (MDR1) Gene Polymorphism and Unresponsiveness Combined Therapy in Chronic Hepatitis C virus

“…They also claimed that the infected patients by mutated virus showed increased incidence of HCC. Viral drug unresponsiveness is sometimes based on viral and/or bacterial gene recombinations, and resistance to the wide range of drugs (29, 40-42) but in general it is based on genomic variation and/or mutations of host organisms genome, intracellular functions and causes different tissue cancers in human (43-47). As claimed by Hoofnagle et al, the racial difference (variation in host genome) takes crucial role in the response to antiviral therapy (48).…”

“…Variation in exon 26 of MDR1 gene also shows significant differences for drug transport. Therefore it affects both response and therapeutic doses of multiple drugs (22-24, 29). The homozygous C alleles in C3435T SNP are considered to be responsible for resistance against the medicines in which the P-gp expression is high and against some materials.…”

“…MDR1 gene was simultaneously amplified and biotin-labeled in a single multiplex amplification reaction (Viennalab, Strip Assay GmbH, Austria). PCR for MDR1 gene was performed in a Perkin Elmer 9600, (Singapore), and the protocol consisted of an initial melting step of 2 min at 95°C; followed by 35 cycles of 15s at 95°C, 30s at 56°C, and 30s at 72°C; and a final elongation step of 3 min at 72°C (29). …”

MDR1 Gene Polymorphisms Are Associated with Glucocorticoid-Induced Avascular Necrosis of the Femoral Head in a Chinese Population

“…The polymorphisms C1236T and C3435T do not change the amino acid, while G2677T/A induces the replacement of amino acid residues (alanine 893-serine 893 or alanine 893-threonine 893). These three SNPs have previously been shown to be associated with both disease development and drug response in different populations (Balcerczak et al, 2010;Ozen et al, 2011;Chen et al, 2012).…”