Research Information System
GENE, no.2, pp.333-339, 2012 (SCI-Expanded)
Behcet's disease (BD) is a chronic multisystem disorder. Infectious agents, immune system mechanisms, and genetic factors are implicated in the etiopathogenesis of BD, which remains to be explained. The human MDR1 (ABCB1) gene encoder P-glycoprotein (P-gp) plays a key role in drug disposition, serves as a protective mechanism against xenobiotics, and provides additional protection for the brain, testis, and fetus. We investigated the genotype and haplotype distributions of three MDR1 gene polymorphisms (C1236T, G2677T/A, and C3435T) in 104 BD patients and 130 control subjects. The genotyping analysis was performed by using PCR-RFLP methods. No statistically significant differences were found for the genotypic and allelic distributions of three individual single nucleotide polymorphisms (SNPs) in the MDR1 gene between BD patients and control subjects in this study (p > 0.05). However, combined genotype and haplotype frequencies have found statistically significant differences between BD and control subjects for some combinations (p < 0.05). The CC-GG binary genotype for C1236T-G2677T/A loci couple in particular may have a high degree of predisposition to BD (p = 0.009: OR, 3.03; 95% CI, 1.41-6.54). Furthermore, significant differences between colchicine-responsive and -nonresponsive groups were found. Genotypic and allelic distributions of C3435T and G2677T/A loci, as well as their genotype and haplotype combinations, were found to have statistically significant differences (p<0.05). The TT genotype for the C3435T locus (p = 0.001; OR, 6.59; 95% CI, 1.86-23.30) and T allele (p= 0.009; OR, 2.09; 95% CI, 1.18-3.70) plays a substantial role in the colchicine response. Our study showed that MDR1 genes and their polymorphisms may affect a patient's BD susceptibility and colchicine response. (c) 2012 Elsevier B.V. All rights reserved.