Transcription regulatory polymorphism -43T>C in the 5'-flanking region of SLC19A1 gene could affect rheumatoid arthritis patient response to methotrexate therapy
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Ημερομηνία
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Rheumatol Int
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
The reduced folate carrier (RFC) protein (SLC19A1-gene) has central role in the uptake and intracellular accumulation of folates. In this respect, we investigate whether SLC19A1 genetic variations could affect rheumatoid arthritis (RA) patient response to antifolate treatment. One hundred six unrelated RA patients were enrolled in this study. Polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) was used as the screening method for genetic variants. Unusual SSCP patterns were characterized by direct sequencing of the PCR products and subsequently restriction assays were established. Western blot analysis of RFC protein was performed in respect of the identified SLC19A1 genotypes. Patient response to methotrexate (MTX) was evaluated using disease activity for 28 joint indices score, American College of Rheumatology 20% and 50% scores. No mutation was found in the SLC19A1 gene, but three polymorphic variants: the -43T>C in the 5'-flanking sequence to the ATG-transcription start site; and the 80G>A (R27H) and 696C>T (P232P) in the coding gene sequence. The wild type alleles of the three polymorphisms were in strict linkage disequilibrium. Western blot analysis revealed that the non-wild type allele of polymorphism -43T>C is associated with low RFC protein expression levels. Furthermore, the genotypic analysis of the functional polymorphic variant -43T>C revealed to be insufficient to predict patient response to MTX therapy. According to recent literature, several transport systems account for folate membrane transport. Additionally, in previous studies discrepancies have been reported to exist between the same genetic variants and their use in prediction of patient response to MTX therapy. Therefore, the present genotypic-phenotypic association study of a functional polymorphism revealed the need of a complex genotypic analysis in order to predict patient response to folate antagonists' therapy.
Περιγραφή
Λέξεις-κλειδιά
Aged, Arthritis, Rheumatoid/drug therapy/genetics, Cohort Studies, Female, Folic Acid Antagonists/ pharmacology, Humans, Male, Membrane Transport Proteins/ genetics/ metabolism, Methotrexate/ pharmacology, Middle Aged, Polymorphism, Single Nucleotide/genetics, Reduced Folate Carrier Protein, Regulatory Elements, Transcriptional/ genetics, Treatment Failure
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://link.springer.com/content/pdf/10.1007%2Fs00296-007-0339-0.pdf
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής