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Effect of MDR1 Gene Polymorphisms on Mortality in Paraquat Intoxicated Patients

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Journal Sci Rep
Specialty Science
Date 2016 Aug 23
PMID 27545861
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Abstract

Paraquat is a fatal herbicide following acute exposure. Previous studies have suggested that multidrug resistance protein 1 (MDR1) might help remove paraquat from the lungs and the kidney. MDR1 single-nucleotide polymorphisms (SNPs) are involved in the pharmacokinetics of many drugs. The purpose of this study was to determine whether MDR1 SNPs were associated with the mortality in paraquat intoxicated patients. We recruited 109 patients admitted with acute paraquat poisoning. They were genotyped for C1236T, G2677T/A, and C3435T single-nucleotide polymorphisms (SNPs) of MDR1 gene. Their effects on mortality of paraquat intoxicated patients were evaluated. Overall mortality rate was 66.1%. Regarding the C1236T of the MDR1 gene polymorphism, 21 (19.3%) had the wild type MDR1 while 88 (80.7%) had homozygous mutation. Regarding the C3435T MDR1 gene polymorphism, 37(33.9%) patients had the wild type, 23 (21.1%) had heterozygous mutation, and 49 (45.0%) had homozygous mutation. Regarding the G2677T/A MDR1 gene polymorphism, 38 (34.9%) patients had the wild type, 57 (52.3%) had heterozygous mutation, and 14 (12.8%) had homozygous mutation. None of the individual mutations or combination of mutations (two or three) of MDR1 SNP genotypes altered the morality rate. The mortality rate was not significantly different among SNP groups of patients with <4.0 μg/mL paraquat. In conclusion, MDR1 SNPs have no effect on the mortality rate of paraquat intoxicated patients.

References
1.
Chang S, Lu T, Eddleston M, Konradsen F, Sterne J, Lin J . Factors associated with the decline in suicide by pesticide poisoning in Taiwan: a time trend analysis, 1987-2010. Clin Toxicol (Phila). 2012; 50(6):471-80. DOI: 10.3109/15563650.2012.688835. View

2.
Silva R, Sousa E, Carmo H, Palmeira A, Barbosa D, Gameiro M . Induction and activation of P-glycoprotein by dihydroxylated xanthones protect against the cytotoxicity of the P-glycoprotein substrate paraquat. Arch Toxicol. 2014; 88(4):937-51. DOI: 10.1007/s00204-014-1193-y. View

3.
Asakura T, Imai A, Ohkubo-Uraoka N, Kuroda M, Iidaka Y, Uchida K . Relationship between expression of drug-resistance factors and drug sensitivity in normal human renal proximal tubular epithelial cells in comparison with renal cell carcinoma. Oncol Rep. 2005; 14(3):601-7. View

4.
Silva R, Vilas-Boas V, Carmo H, Dinis-Oliveira R, Carvalho F, Bastos M . Modulation of P-glycoprotein efflux pump: induction and activation as a therapeutic strategy. Pharmacol Ther. 2014; 149:1-123. DOI: 10.1016/j.pharmthera.2014.11.013. View

5.
Choi J, Lee Y, Jang S, Lee J, Kim K, Park K . Influence of the CYP3A5 and MDR1 genetic polymorphisms on the pharmacokinetics of tacrolimus in healthy Korean subjects. Br J Clin Pharmacol. 2007; 64(2):185-91. PMC: 1974827. DOI: 10.1111/j.1365-2125.2007.02874.x. View