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MDR1 gene polymorphism in Japanese patients with schizophrenia and mood disorders including depression.

Abstract：

:P-Glycoprotein (ABCB1-type P-gp), a membrane protein encoded by the multi drug resistant gene (MDR1), expressing on the blood brain barrier protects the brain from many drugs including dexamethasone. Psychiatric disorders, schizophrenia and depression, have known to have abnormal hypothalamus-pituitary-adrenal (HPA) activity, which is assessed by non-suppression of cortisol in dexamethasone suppression test. The poor response to dexamethasone in these patients' population suggested the impaired activity on dexamethasone penetration into the brain via P-gp, which was associated with MDR1 polymorphisms. We, therefore, examined five SNPs of the MDR1 gene, -1517 T>C (promoter), -41 A>G (intron -1), -129 T>C (exon 1b), 2677 G>A,T (exon 21) and 3435 C>T (exon 26), in Japanese patients with schizophrenia (n=121) and mood disorders (n=62), and compared with the control subjects (n=160). The frequency of MDR1 mutant alleles at -1517, -41 and -129 in patients with mood disorders was significantly lower (2.4, 5.6, 2.4%, respectively) than those of controls (7.8, 13.7, 7.8%, respectively) (p<0.05). The frequencies of MDR1 2677 G/A and A/A genotype in mood disorders was significantly higher (17.7, 6.5%, respectively) than controls (11.2, 0%, respectively) (p<0.05). The 2677A allele frequency in mood disorders (20.2%) was significant higher than controls (10.9%) (p<0.05). Haplotype of 129-2677-3435 (T-A-C) in mood disorders was significantly higher (14.4%) than controls (8.0%) (p<0.05). There was no significant difference in allele and genotype frequencies between the patients with schizophrenia and controls. These findings suggested that predispose to mood disorders, not schizophrenia, was associated with possible alteration of P-gp activities corresponding MDR1 polymorphism at least partly.

journal_name

Biol Pharm Bull

journal_title

Biological & pharmaceutical bulletin

authors

Qian W,Homma M,Itagaki F,Tachikawa H,Kawanishi Y,Mizukami K,Asada T,Inomata S,Honda K,Ohkohchi N,Kohda Y

doi

10.1248/bpb.29.2446

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

2446-50

issue

eissn

0918-6158

issn

1347-5215

pii

JST.JSTAGE/bpb/29.2446

journal_volume

pub_type

杂志文章

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MDR1 gene polymorphism in Japanese patients with schizophrenia and mood disorders including depression.