Cry1 and Tef gene polymorphisms are associated with major depressive disorder in the Chinese population

doi:10.1016/j.jad.2013.11.019

Journal of Affective Disorders

Volume 157, 20 March 2014, Pages 100-103

https://doi.org/10.1016/j.jad.2013.11.019 Get rights and content

Abstract

Introduction

Accumulating evidences indicate that circadian abnormalities lead to sleep disorder, neurodegenerative diseases and depression. We have reported that the polymorphisms of a clock-related gene, Tef, contributed to the risk of sleep disturbances and depression in the Parkinson disease. The objective of the present study was to examine whether the three clock genes we previously studied are associated with major depressive disorder (MDD) in the Chinese population.

Methods

105 Subjects with MDD and 485 control subjects participated in this case-control study. Demographics, Mini-mental Status Examination (MMSE), and the Hamilton rating scale for depression (HAMD) were obtained in all subjects. Genotypes of single nucleotide polymorphisms (SNPs) of Cry1 rs2287161, Cry2 rs10838524 and Tef rs738499 were screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results

MDD cases had a significantly higher frequency carrying the C allele and CC genotype in Cry1 rs2287161 and the T allele and TT genotype in Tef rs738499 than controls.

Limitations

The sample size of MDD group was relatively small.

Conclusions

The polymorphisms of Cry1 rs2287161 and Tef rs738499 are associated to MDD.

Introduction

Circadian effects on depression are presented in four areas. First, the physiological and behavioral abnormalities in depression are associated with circadian dysfunction, such as abnormal temperature rhythms, disturbed sleep, disregulated hormonal secretion, and a repetitive pattern of diurnal mood cycle (Bunney and Potkin, 2008). Second, chronobiological interventions on patients with depression, such as sleep deprivation, light therapy, or combining with sleep phase advance, can dramatically improve their depressive symptoms within hours (Wu and Bunney, 1990, Fritzsche et al., 2001, Dallaspezia and Benedetti, 2011). Third, the effects of traditional antidepressants such as fluoxetine and lithium, might exert their effects via regulating circadian-related mechanisms (Sprouse et al., 2006, Abe et al., 2000). Fourth, agomelatine, a melatonergic agonist, is developed on the basis of resynchronising the circadian rhythms, and agomelatine has been demonstrated to be effective to treat depression (Zajecka et al., 2010, Kasper et al., 2010). Based on the above, the relationship between circadian rhythm and depression is of great interests.

The circadian rhythm is maintained by the clock genes networks consisting of a series of auto-regulatory transcription–translation loops with positive and negative feedbacks to core clock genes and their proteins (Takahashi et al., 2008). Several core clock genes have been characterized including the cryptochrome genes (Cry1, 2), the period genes (Per1, 2, 3), and the genes Clock (Npas2) and Bmal1. Some other clock-related genes are also involved in the regulation of circadian rhythmicity, such as Tef, Vip, AANAT, Sirl1, Prock2, Timeless, and so on. A few studies have reported that several clock gene polymorphisms were associated with certain subtypes of depression including seasonal affective disorder (SAD), major depressive disorder (MDD) and bipolar disorder (BPD). Soria et al. (2010a) reported that Cry1 rs2287161 and Npas2 rs11123857 were associated with MDD, and Clock rs10462028 and Vip rs17083008 were associated with BPD. Soria et al. (2010b) also presented evidence of the association of genetic polymorphism in the AANAT gene with susceptibility to MDD. Lavebratt et al. (2010) found the Cry2 rs10838524 was significantly associated with SAD; and a recent study by Kovanen et al. (2013) demonstrated several SNPs including rs10838524 to be related to dysthymia. Tef rs738499 was suggested to be a risk factor to unipolar major depression (Kripke et al., 2009), and in a replication study (Kripke et al., 2010), Tef rs738499 was also associated with the depressive symptoms in the sleep clinic patients. Sirt1 (Kishi et al., 2010a) and Prock2 (Kishi et al., 2010b) genes were reported to associate with MDD in Japanese population. These reported risk clock gene polymorphisms have been individually studied to be associated with depression; however, no replication studies have been conducted.

Several clinical studies established a direct correlation between circadian dysfunction and neurodegenerative disease (Kondratova and Kondratov, 2012), we studied three of the above genetic polymorphisms in patients with the Parkinson disease recently. As a result, we found that Tef rs738499 was related to sleep disturbances (Hua et al., 2012a) and depression in the Parkinson disease (Hua et al., 2012b), but no association was found as for Cry1 rs2287161 or Cry2 rs10838524 and depression in the Parkinson disease. It is uncertain whether Tef rs738499 is specific to the Parkinson disease or is associated to primary mood disorder. Therefore, we conducted a case-control study for an association analysis between Cry1 rs2287161, Cry2 rs10838524 and Tef rs738499 and MDD in the Chinese population.

Section snippets

Study subjects

We studied 105 unrelated MDD patients and 485 unrelated healthy controls. MDD patients were recruited from the psychiatry ward of the Affiliated Brain Hospital of Nanjing Medical University between January 2010 and October 2010. They were diagnosed through a structured interview for the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR; APA, 2000) by two experienced psychiatrists. Depression severity was evaluated with the 24-item Hamilton rating scale for depression (HAMD) (

Results

There was no significant difference in age, gender, and MMSE scores between the two groups. The demographic and clinical characteristics of the study subjects are shown in Table 1. A significantly higher frequency of the C allele in Cry1 rs2287161 was found in MDD cases than in controls (OR=1.75, 95% CI: 1.12–2.71, p=0.012). Similarly the MDD cases had a higher frequency of the T allele in Tef rs738499 than controls (OR=2.22, 95% CI: 1.42–3.46, p<0.001) (Table 2). MDD cases are 1.75 times more

Discussion

The main findings in the present study were the associations of Cry1 rs2287161 and Tef rs738499 polymorphisms with MDD. We did not find any significant association between Cry2 rs10838524 and MDD. Therefore, these findings suggested that Cry1 rs2287161 and Tef rs738499 could play a role in the pathogenesis of MDD. Meanwhile, the association with Tef indicated that it was not only a risk factor to depressive symptoms in Parkinson's disease but also a risk factor for MDD. From the linear

Role of funding source

The study was supported by the National Natural Science (81170309), and the Key Project of Medical Science and Technology Development Foundation from Nanjing Department of Health (200905016).

Conflict of interest

The authors report no conflict of interests in this article.

Acknowledgment

We thank all the participants in this study.

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Preliminary communicationCry1 and Tef gene polymorphisms are associated with major depressive disorder in the Chinese population☆

Abstract

Introduction

Methods

Results

Limitations

Conclusions

Introduction

Section snippets

Study subjects

Results

Discussion

Role of funding source

Conflict of interest

Acknowledgment

Curr. Biol.

J. Affect. Disord.

J. Psychiatr. Res.

Sleep Med.

J. Affect. Disord.

Prog. Neuropsychopharmacol. Biol. Psychiatry

J. Affect. Disord.

Biol. Psychiatry

Lithium lengthens the circadian period of individual suprachiasmatic nucleus neurons

Neuroreport

Diagnostic and Statistical Manual of Mental Disorders

Circadian abnormalities, molecular clock genes and chronobiological treatments in depression

Br. Med. Bull.

Population-based norms for the Mini-Mental State Examination by age and educational level

J. Am. Med. Assoc.

Chronobiological therapy for mood disorders

Expert Rev. Neurother.

The mammalian circadian timing system: from gene expression to physiology

Chromosoma

The loss of circadian PAR bZip transcription factors results in epilepsy

Genes Dev.

Preliminary communication
Cry1 and Tef gene polymorphisms are associated with major depressive disorder in the Chinese population☆