GTP cyclohydrolase 1 gene haplotypes as predictors of SSRI response in Japanese patients with major depressive disorder.

Abstract

BACKGROUND:

Tetrahydrobiopterin (BH4) plays an important role in the biosynthesis of serotonin, melatonin and catecholamines, all of which are implicated in the pathophysiology of mood disorders (MDs), including major depressive disorder (MDD) and bipolar disorder (BP). Production of BH4 is regulated by GTP cyclohydrolase transcription and activity. Thus, we considered the GTP cyclohydrolase gene (GCH1) to be a good candidate gene in the pathophysiology of MDs and of the serotonin selective reuptake inhibitors (SSRIs) response in MDD, and conducted a case-control study utilizing three SNPs (rs8007267, rs3783641 and rs841) and moderate sample sizes (405 MDD patients, including 262 patients treated by SSRIs, 1022 BP patients and 1805 controls).

METHOD:

A multiple logistic regression analysis was carried out to compare the frequencies of each SNP genotype for the target phenotype across patients and controls in several genetic models, while adjusting for possible confounding factors. A clinical response was defined as a decrease of more than 50% from the baseline score on the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D) within 8 weeks, and clinical remission as a SIGH-D score of less than 7 at 8 weeks.

RESULT:

No associations between three SNPs in GCH1 and MDD or BP were observed; however, GCH1 was associated with SSRI therapeutic response in MDD in all the marker's haplotype analysis (Global P value=0.0379).

CONCLUSIONS:

Results suggest that GCH1 may predict response to SSRI in MDD in the Japanese population. Nevertheless, a replication study using larger samples may be required for conclusive results, since our sample size was small.

• Authors: Taro Kishi, Hiroshi Ichinose, Reiji Yoshimura, Yasuhisa Fukuo, Tsuyoshi Kitajima, Toshiya Inada, Hiroshi Kunugi, Tadafumi Kato, Takeo Yoshikawa, Hiroshi Ujike, Giovanna M Musso, Wakako Umene-Nakano, Jun Nakamura, Norio Ozaki, Nakao Iwata
• Journal: Journal of affective disorders (J Affect Disord) Vol. 142 Issue 1-3 Pg. 315-22 (Dec 15 2012) ISSN: 1573-2517 [Electronic] Netherlands
• PMID: 22770721 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Antidepressive Agents
• Serotonin Uptake Inhibitors
• GTP Cyclohydrolase
• Fluvoxamine

Topics

• Adult
• Antidepressive Agents (therapeutic use)
• Asian People (genetics)
• Bipolar Disorder (drug therapy, genetics)
• Case-Control Studies
• Depressive Disorder, Major (drug therapy, genetics)
• Female
• Fluvoxamine (therapeutic use)
• GTP Cyclohydrolase (genetics)
• Gene Frequency
• Genotype
• Haplotypes
• Humans
• Logistic Models
• Male
• Middle Aged
• Phenotype
• Polymorphism, Single Nucleotide
• Selective Serotonin Reuptake Inhibitors (therapeutic use)