C3435T Polymorphism of the ABCB1 Gene in Polish Patients with Inflammatory Bowel Disease: A Case–Control and Meta-Analysis Study

Abstract

P-glycoprotein encoded by the ABCB1 gene constitutes a molecular barrier in the small and large bowel epithelium, and its different expression may influence susceptibility to inflammatory bowel disease (IBD). We aimed to assess the contribution of the C3435T polymorphism to disease risk in the Polish population. A total of 100 patients (50 Crohn’s disease (CD), 50 ulcerative colitis (UC)) and 100 healthy controls were genotyped for the single nucleotide polymorphism (SNP) C3435T by using the PCR-RFLP method. Patients were classified on the basis of disease phenotype and the specific treatment used. A meta-analysis was carried out of our results and those from previously published Polish studies. There was no significant difference in allele and genotype frequencies in IBD patients compared with controls. For CD patients, a lower frequency of TT genotype in those with colonic disease, a lower frequency of T allele, and a higher frequency of C allele in those with luminal disease were observed, whereas for UC patients, a lower frequency of CT genotype was observed in those with left-sided colitis. A meta-analysis showed a tendency towards higher prevalence of CC genotype in UC cases. These results indicate that the C3435T variants may confer a risk for UC and influence disease behaviour.

Frequency of ABCB1 C3435T Polymorphism in Rheumatoid Arthritis Patients; Relation to Methotrexate Responsiveness and Methotrexate Adverse Effects

“…RA is a multifactorial disease that is triggered by a combination of genetic predisposition in addition to environmental factors [20] . The C3435T polymorphism has been linked to susceptibility to several diseases including Parkinson's disease [8] , inflammatory bowel disease [9] , ischemic disease [10] , breast cancer [11] , cancer colon [12] , and leukemia [13] .…”

“…The C3435T polymorphism has been linked to susceptibility to several diseases including Parkinson's disease [8] , inflammatory bowel disease [9] , ischemic heart disease [10] , breast cancer [11] , colorectal cancer [12] , and leukemia [13] . The CC genotype of C3435T was also reported to be linked to higher risk of pharmacoresistance to a wide range of drugs including antiepileptics [14] , antipsychotics, antidepressants [15] , glucocorticoids [16] and methotrexate [17] .…”

The roles of ABCB1/P-glycoprotein drug transporters in regulating gut microbes and inflammation: insights from animal models, old and new

“…To explain this contradiction, they proposed a potential linkage disequilibrium between SNPs in exon 26 (C3435T) and exon 21 (G2677T/A). This suggests that the observed differences in ABCB1 expression initially attributed to the exon 26 SNP might actually be the result of the associated tri-allelic polymorphism in exon 21 [ 60 ].…”

Multi-omics in Crohn's disease: New insights from inside

“…The polymorphisms of substantial genes such as ATG16L1 , IL-23R gene and fucosyltransferase 2 gene are identified to be relevant to the susceptibility to CD, attributing the success to the massive meta-analyses of CD genome-wide association studies [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] . Several GWAS studies have demonstrated that SNPs in the immunity-related GTPase family M ( IRGM ) and the deletion polymorphism of the IRGM promoter region are closely related to CD.…”