Association of Genetic Polymorphisms of Multidrug Resistance Protein (MDR) with Clinical Outcomes in Colchicine Intoxication
Objectives: The current study aimed to investigate the question that if the genetic polymorphisms of MDR1 could be a contributing factor in prognosis of colchicine poisoned patients. For this purpose, we examined clinically significant MDR1 genetic polymorphisms in patients with colchicine intoxication and their relationship with treatment outcomes.
Methods: MDR1 polymorphisms were studied in the blood samples collected from patients with intake of subtoxictoxic-lethal doses of colchicine before plasma or whole blood exchange between years 2013- 2018. Results: A total of 17 patients were included in the study. Median age was 15 years (min:1-max:17). Mean dose of colchicine was 0.52±0.2 mg/kg. Activated charcoal and gastric lavage was performed to all of the patients and granulocyte colony stimulating factor was given to 8 (47.1 %) patients. Two (11.8 %) of the 17 patients died. Whole blood exchange was performed in 11 ( 64.7%) patients. Extracorporeal membrane oxygenation was performed to 2 (11.8%) patients. For 1236C>T genotypes, wild type, heterozygous (CT) and homozygous mutant genotypes were demonstrated in 1 (5.9%), 11 (64.7%) and 5 (29.4%) patients, respectively. For 2677G>T/A genotype heterozygous (GT) and homozygous mutant (TT) genotypes were demonstrated in 10 (58.8 %) and 7 (41.2%) patients respectively. For 3435C>T polymorphism, wild type, heterozygous (CT) and homozygous genotypes were demonstrated in 1 (0.9 %), 10 (58.8%) and 6 (35.3%) patients, respectively. Five (29.4%) out of 17 patients had combined TT-TT-TT homozygous genotypes for the polymorphisms of MDR11236C>T, 2677G>T/A, 3435C>T and two of these five patients died. The rate (40%) of died two patients carrying homozygous (TT-TT-TT) mutant haplotypes compared with rate (0%) of none of died twelve patients having heterozygous (CT or GT) mutant haplotypes was borderline significant (40% vs 0%, p=0.07).
Conclusion: Two patients who died due to colchicine intoxication were homozygous carriers of the variant alleles wi
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