title: Effect of MDR1 gene polymorphisms on mortality in paraquat intoxicated patients.
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.
authors.affiliation: Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Choongcheongnam-do 330-930, Republic of Korea.
authors.forename: Hak Jae
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Choongcheongnam-do 330-930, Republic of Korea.
authors.forename: Hyung-Ki
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Choongcheongnam-do 330-930, Republic of Korea.
authors.forename: Jun-Tack
authors.initials: JT
authors.lastname: Kwon
authors.affiliation: Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea.
authors.forename: Sun-Hyo
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea.
authors.forename: Sam
authors.initials: S
authors.lastname: El Park
authors.affiliation: Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea.
authors.forename: Hyo-Wook
authors.initials: HW
authors.lastname: Gil
authors.affiliation: Department of Microbiology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea.
authors.forename: Ho-Yeon
authors.initials: HY
authors.lastname: Song
authors.affiliation: Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea.
authors.forename: Sae-Yong
authors.initials: SY
authors.lastname: Hong
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000208:Acute Disease; D000328:Adult; D000368:Aged; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010269:Paraquat / Q000506:poisoning*; D011041:Poisoning / Q000235:genetics* / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D015996:Survival Rate
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D010269:Paraquat