A common P-glycoprotein polymorphism is associated with nortriptyline-induced postural hypotension in patients treated for major depression

被引：147

作者：

Roberts R.L. ^{[1
]}

Joyce P.R. ^{[1
]}

Mulder R.T. ^{[1
]}

Begg E.J. ^{[1
]}

Kennedy M.A. ^{[1
]}

机构：

[1] Department of Pathology, Christchurch School of Medicine, Christchurch

来源：

The Pharmacogenomics Journal | 2002年 / 2卷 / 3期

关键词：

ABC transporters; ABCB1; Affective disorders; Antidepressants; Fluoxetine; Multidrug resistance gene MDR1; Pharmacogenetics;

D O I：

10.1038/sj.tpj.6500099

中图分类号：

学科分类号：

摘要：

The multi-drug resistance gene ABCB1 (or MDR1) encodes a P-glycoprotein (P-gp) that regulates passage of many substances across the blood-brain barrier. The antidepressant amitriptyline and its metabolites (including nortriptyline) are substrates for P-gp, and in mice lacking P-gp, penetration of amitriptyline, but not fluoxetine, into the brain is enhanced. We reasoned that polymorphic variation of P-gp may contribute to differing responses of patients to antidepressant drugs. A single nucleotide polymorphism (SNP) of ABCB1 (3435C>T) was recently correlated with expression levels and in vivo function of P-gp. We examined this SNP in patients with major depression enrolled in a randomized antidepressant treatment trial of nortriptyline and fluoxetine, and observed a significant association between nortriptyline-induced postural hypotension and 3435C>T (X2 = 6.78, df = 2, P = 0.034). Our results suggest that homozygosity for 3435T alleles of ABCB1 is a risk factor for occurrence of nortriptyline-induced postural hypotension (OR = 1.37, P1.37, P = 0.042, 95% Cl 1.01-1.86).

引用

页码：191 / 196

页数：5

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