Genotype and haplotype analysis ofABCB1at 1236, 2677 and 3435 among systemic sclerosis patients

Abstract

Systemic sclerosis (SSc) belongs to the group of systemic diseases of the connective tissue, which are characterized by a chronic autoimmune inflammatory process. P-glycoprotein, initially associated with the drug resistance in patients with cancer, becomes more and more often a subject of considerations in terms of its significance in the development of illnesses, including autoimmune diseases. The aim of the study was an attempt to answer the question whether there was a relationship between ABCB1 polymorphisms and morbidity of systemic sclerosis in a Polish population. The study was carried out in 61 patients with SSc and 100 healthy volunteers. Determination of polymorphisms C1236T and C3435T in ABCB1 was carried out with the PCR-RFLP (polymerase chain reaction - restriction fragment length polymorphism) method. The G2677T/A ABCB1 polymorphism was analysed with the allele-specific PCR method. No statistically significant differences were observed in the frequencies of ABCB1 genotypes and alleles between SSc patients and the control group. It was observed that haplotype 1236 C-2677 G-3435 T occurred in the group of patients with SSc statistically more frequently than in the group of healthy volunteers (25% vs. 15%; p = .032). Carriers of the haplotype demonstrated almost a twofold greater risk of SSc (OR = 1.85; p = .032). No statistically significant correlations for the other nine haplotypes were found. Presented results concerning the relationship of ABCB1 polymorphisms with susceptibility to systemic sclerosis are the first ones that were obtained in a Polish population. They imply that single nucleotide polymorphisms do not affect the risk for SSc, but the 1236 C-2677 G-3435 T haplotype might increase this risk.

Peripheral Hybrid CB1R and iNOS Antagonist MRI-1867 Displays Anti-Fibrotic Efficacy in Bleomycin-Induced Skin Fibrosis

“…A recent study compared the frequencies of 3 single nucleotide polymorphisms (SNPs) in the ABCB1 gene, which encodes P-gp, and found no differences between patients with systemic sclerosis and their controls in a Polish population. Although a specific haplotype of these SNPs occurred significantly more frequently among patients than among their controls, there was no evidence presented for an association of this haplotype with altered gene or protein expression or transporter activity of ABCB1 ( 30 ).…”

Haplotypes of ABCB1 1236C >T (rs1128503), 2677G >T/A (rs2032582), and 3435C >T (rs1045642) in patients with bullous pemphigoid

“…Consequently, the study determined that individuals with the haplotype have a nearly twofold higher risk of developing SSc (OR = 1.85, 95% CI 1.05–3.25, p  = 0.032) [5]. …”

“…In available literature, one can find papers on the role of ABCB1 polymorphisms in dermatologic diseases with an autoimmune background, which pemphigoid is classified as [ 5 , 8 , 9 , 11 , 37 , 38 ]. Autoimmune diseases belong to chronic disorders with unknown etiology, characterized by a broad spectrum of immune system abnormalities.…”

“…A haplotype analysis of ABCB1 , which had been conducted in patients with systemic sclerosis (SSc) in Poland, revealed a statistically significantly higher frequency of the 1236C-2677G-3435T haplotype in the SSc group in comparison with the control group (25 vs. 15%, p = 0.032). Consequently, the study determined that individuals with the haplotype have a nearly twofold higher risk of developing SSc (OR = 1.85, 95% CI 1.05–3.25, p = 0.032) [ 5 ].…”

“…Genetic polymorphisms of P-gp might affect not only the effectiveness of treatment with drugs that are P-gp substrates, but also contribute to the development of diseases [ 2 , 5 , 9 , 27 , 32 , 44 , 45 ].…”