- Email: [email protected]
Single nucleotide polymorphisms and mRNA expression for melatonin MT2 receptor in depression
Psychiatry Research 189 (2011) 472–474
Contents lists available at ScienceDirect
Psychiatry Research j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / p s yc h r e s
Brief report
Single nucleotide polymorphisms and mRNA expression for melatonin MT2 receptor in depression Elżbieta Gałecka a, Janusz Szemraj b, Antoni Florkowski c, Piotr Gałecki c, Małgorzata Bieńkiewicz d, Małgorzata Karbownik-Lewińska e,f, Andrzej Lewiński a,f,⁎ a
Department of Endocrinology and Metabolic Diseases, Medical University of Łódź, Poland Department of Medical Biochemistry, Medical University of Łódź, Poland Department of Adult Psychiatry, Medical University of Łódź, Poland d Department of Quality Control and Radiological Protection, Medical University of Łódź, Poland e Department of Oncological Endocrinology, Medical University of Łódź, Poland f Polish Mother's Memorial Hospital, Research Institute, Łódź, Poland b c
a r t i c l e
i n f o
Article history: Received 27 May 2010 Received in revised form 24 January 2011 Accepted 27 January 2011 Keywords: Melatonin MT2 receptor Polymorphism Depression
a b s t r a c t Polymorphisms (rs 4753426 and rs 794837) and expression of the melatonin MT2 receptor gene were evaluated in 181 patients with recurrent depressive disorder (rDD) and 149 healthy subjects of Polish origin. We found an increased risk for rDD in patients with the C allele and a decreased risk in patients with the T allele (rs4753426). Patients with the AT heterozygote (rs794837) had an increased mRNA level. The significance of the MT2 receptor gene and the risk of rDD are suggested. © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Melatonin modulates numerous processes via the MT2 membrane receptor expressed in such brain regions as the suprachiasmatic nucleus (SCN), the cerebellum and the hippocampus (Pandi-Perumal et al., 2008). Activation of the MT2 receptor induces phase-shifts in the electrical activity of SCN neurons and hence results in entrainment of circadian rhythms (Pandi-Perumal et al., 2008). The significance of the MT2 receptor has been demonstrated in neural plasticity (Wang et al., 2005) and neuron protection. The expression of MT2 receptors and their modulatory role were also revealed in cells of the immune system (Lardone et al., 2009). The gene – encoding the MT2 receptor is located at 11q21-22 chromosome (Reppert et al., 1995). For that gene single nucleotide polymorphisms (SNPs), rs4753426 and rs794837, located in the 5′-flanking region, have been described. Both SNPs are in the promoter region. In addition, the rs4753426 SNP located in the regulatory region and the DNA sequence around this site possibly constitute a binding site for one of the transcription factors (Qiu et al., 2007). We studied the relationship between the gene for MT2 receptor polymorphisms and/or gene expression (transcript level), and the risk of recurrent depressive disorder (rDD) risk.
2. Methods 2.1. Subjects A group of 181 patients (102 females—56.4%; mean age 42.6 ± 8.2 years), treated for rDD in the Department of Adult Psychiatry (Medical University of Lodz, Central Poland) meeting the ICD-10 criteria (F33.0–F33.8) (World Health Organization, 1992) and 149 healthy subjects (83 females—55.7%; mean age 38.7 ± 6.7 years) were enrolled into the study. No significant differences were found between the analyzed groups with respect to either age (P N 0.05) or gender (P N 0.05) (Supplementary material). An informed consent was obtained from all the participants of the study. The study protocol was approved by the Local Bioethics Committee No. RNN/626/09/KB.
2.2. Statistical analysis The results are reported as percentages (%) or means with standard deviations (±S.D.). To examine the association between the genotype distribution and rDD, χ2 test—genotypic model was used. Post-hoc power analysis was performed with the use of non-central χ2 distribution. The analysis of association was based on the 95% confidence interval (CI) for the disease odds ratio (ORdis), calculated with the use of a logistic regression model including sex and age as covariates. MT2 gene expression levels were compared by appropriate nonparametric tests: Mann–Whitney's or Kruskal-Wallis. For all the analyses Statistica 8.0 was used and, P ≤0.05 was accepted as the level of statistical significance.
2.3. Procedures ⁎ Corresponding author at: Department of Endocrinology and Metabolic Diseases, Medical University of Łódź, Poland, 281/289, Rzgowska St., PL 93–338 Łódź, Poland. Tel.: +48 42 2711705; fax: +48 42 2711343. E-mail address: [email protected] (A. Lewiński). 0165-1781/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2011.01.021
The genotyping was performed using 0.1 μg of genomic DNA and specific primers for rs4753426 and rs794837 SNPs. The amplification products were digested with restriction enzymes Hae III, Eco NI (New England, BioLabs) respectively and separated on polyacrylamide gel.
E. Gałecka et al. / Psychiatry Research 189 (2011) 472–474 We evaluated a few housekeeping genes from different abundance and functional classes like the beta-actin, GAPDH, HPRT and 18S rRNA genes as endogenous controls. We rejected the beta-actin, GAPDH and HPRT genes because of the existence of corresponding retropseudogenes. The gene for the MT2 receptor and 18S rRNA gene expression was quantified by real-time PCR, using an ABI Prism 7000 Sequence Detection System (Applied Biosystems, Foster City, CA, USA), according to the manufacturer's protocol. Relative gene expression level was normalized to a normal blood sample (calibrator) and was obtained using the ΔΔCt method. Amplification – specific transcripts were further confirmed by melting curve profiles.
3. Results Distribution of genotype frequencies and the Hardy–Weinberg equilibrium in rDD patients and controls were in the following correlation; rs4753425: rDD—χ2 =2.26; controls—χ2 =3.58; rs794837: recurrent DD—χ2 =0.0001; controls—χ2 =3.197. Data and statistical analyses regarding genotype distribution, allele frequency and ORdis values, with age and sex as covariates determined with respect to the rs4753426 and rs794837 SNPs of the MT2 gene are presented in Table 1. Analysis of allele frequency with the use of logistic regression demonstrated that the presence of the C (rs4753426) allele increased rDD risk, whereas the presence of the T (rs4753426) allele decreased the risk in question. Both in the group of patients and in controls, the level of mRNA transcript was significantly different, depending on the genotype (for both examined SNPs, Kruskal-Wallis' test, P b 0.0001). Patients with the AT heterozygote (rs794837) compared with controls had an increased mRNA level (Table 1). No significant differences in the mRNA expression for particular alleles between rDD patients and healthy subjects (rs4753426, P = 0.93 and rs794837, P = 0.17, respectively) were found: 0.063 ± 0.008 (rDD; n = 181) vs 0.061 ± 0.007 (controls; n = 149).
473
Our results are partially supported by earlier findings. Chromosome 11 – at which the gene for the MT2 receptor is mapped – should be of interest in investigations of the gene(s) that are likely to participate in the etiology of depression (Kolomietz et al., 2006). Our results are in line with antidepressant properties of the MT2 receptor antagonist (Sumaya et al., 2005), due to the fact that receptors are expressed in the hippocampus (Musshoff et al., 2002) and participate in the reduction of synaptic plasticity and cell excitability (Hogan et al., 2001). There are also data from animal studies indicating that genetic variants within the MT2 receptor gene may determine its expression (Xiao et al., 2007). Investigated SNPs are located in the promoter region and are in linkage disequilibrium (LD), but we have found that only rs 794837 is related to mRNA expression but rs 4753426 determines the risk of depression. Such results suggest the possibility of these variants being in linkage disequilibrium with other locus conferring susceptibility to depression. An association with the MT2 receptor gene polymorphism was discovered in patients with rheumatoid arthritis (RA) (Ha et al., 2005). Such results may suggest that inflammation and depression have common genes. A role of the MT2 receptor in the mechanism of memory processes and neuronal plasticity as well as its contribution to sleep disorders and neuroprotection was also reported (Larson et al., 2006; Pandi-Perumal et al., 2008). In drawing conclusions from the study, we may cautiously suggest that the MT2 receptor gene may play a role in determining the risk for rDD with a possible unfavorable role of the AT heterozygote in the rs794837 polymorphism. Concerning the rs 4753426 SNP, the C allele may constitute a risk factor, and the T allele is suggested as a protective factor against rDD. Appendix A. Supplementary material Supplementary data to this article can be found online at doi:10.1016/j.psychres.2011.01.021.
4. Discussion To the best of our knowledge, the reported study is the first one investigating SNPs and mRNA expression of the MT2 receptor gene in rDD. Additionally, a gene related to melatonin synthesis (rate-limiting enzyme) was suggested as a susceptibility gene for rDD (Gałecki et al., 2010). We demonstrated that the genetic variants influence the risk for rDD. The obtained data may also indicate that a possible increase of mRNA for the MT2 receptor gene could be, considering some loci, genotype – dependent.
References Gałecki, P., Szemraj, J., Bartosz, G., Bieńkiewicz, M., Gałecka, E., Florkowski, A., Lewiński, A., Karbownik-Lewińska, M., 2010. Single nucleotide polymorphisms and mRNA expression for melatonin synthesis rate limiting enzyme in recurrent depressive disorder. Journal of Pineal Research 48, 311–317. Ha, E., Choe, B.K., Jung, K.H., Yoon, S.H., Park, H.J., Park, H.K., Yim, S.V., Chung, J.H., Bae, H.S., Nam, M., Baik, H.H., Hong, S.J., 2005. Positive relationship between melatonin receptor type 1B polymorphism and rheumatoid factor in rheumatoid arthritis patients in the Korean population. Journal of Pineal Research 39, 201–205.
Table 1 Genotype distribution, allele frequency of MT2 receptor gene polymorphisms (rs4753426 and rs794837), odds ratio of the disease (age and sex adjusted by logistic regression) for both polymorphisms and MT2 receptor mRNA expression regarding rs794837. MT2 receptor rs4753426 Genotype
CC
rDD n; (%) Controls n; (%) Statistical analysis; Post-hoc power analyses
92; (50.83) 81; (44.75) 8; (4.42) 61; (40.94) 75; (50.34) 13; (8.72) 2 χ —4.64; d.f. = 2; P = 0.098; Effect size w = 0.23; n = 330; power 1-β = 99%
CT
TT
−C 265; (73.2) 197; (66.1) ORdis for − C allele: 1.42; (95% CI = 1.01–2.01) ORdis for − T allele: 0.70; (95% CI = 0.50–0.99), P = 0.046
MT2 receptor rs794837 Genotype
AA
AT
TT
rDD n; (%) Controls n; (%) Statistical analysis; Post hoc power analysis
33; (18.23) 102; (56.35) 46; (25.42) 31; (20.81) 74; (49.66) 44; (29.53) 2 χ —1.47; d.f. = 2; P = 0.48; Effect size w = 0.13; n = 330; power 1-β = 76%
−A 168; (46.4) 136; (45.6) ORdis for − A allele: 1.06; (95% CI = 0.77–1.47) ORdis for − T allele: 0.94; (95% CI = 0.68–1.30), P = 0.71
MT2 receptor mRNA expression (rs794837) Genotype
AA
AT
TT
rDD (n) ± S.D. Controls (n) ± S.D.
(33) 0.064 ± 0.007 (31) 0.063 ± 0.007 P N 0.05
(102) 0.065 ± 0.008 (74) 0.062 ± 0.006 P = 0.02
(46) 0.057 ± 0.007 (44) 0.057 ± 0.006 P N 0.05
rDD—patients with recurrent depressive disorder; ORdis—odds ratio of the disease; 95% CI—95% confidence interval, P—level of statistical significance.
474
E. Gałecka et al. / Psychiatry Research 189 (2011) 472–474
Hogan, M.V., El-Sherif, Y., Wieraszko, A., 2001. The modulation of neuronal activity by melatonin: in vitro studies on mouse hippocampal slices. Journal of Pineal Research 30, 87–96. Kolomietz, E., Ben-Omran, T., Chitayat, D., Mah, M., Murphy, J., Nie, G., Teshima, I., 2006. Array-based genomic delineation of a familial duplication 11q14.1-q22.1 associated with recurrent depression. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics 141B, 214–219. Lardone, P.J., Carrillo-Vico, A., Molinero, P., Rubio, A., Guerrero, J.M., 2009. A novel interplay between membrane and nuclear melatonin receptors in human lymphocytes: significance in IL-2 production. Cellular and Molecular Life Sciences: CMLS 66, 516–525. Larson, J., Jessen, R.E., Uz, T., Arslan, A.D., Kurtuncu, M., Imbesi, M., Manev, H., 2006. Impaired hippocampal long-term potentiation in melatonin MT2 receptordeficient mice. Neuroscience Letters 393, 23–26. Musshoff, U., Riewenherm, D., Berger, E., Fauteck, J.D., Speckmann, E.J., 2002. Melatonin receptors in rat hippocampus: molecular and functional investigations. Hippocampus 12, 165–173. Pandi-Perumal, S.R., Trakht, I., Srinivasan, V., Spence, D.W., Maestroni, G.J., Zisapel, N., Cardinali, D.P., 2008. Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Progress in Neurobiology 85, 335–353.
Qiu, X.S., Tang, N.L., Yeung, H.Y., Lee, K.M., Hung, V.W., Ng, B.K., Ma, S.L., Kwok, R.H., Qin, L., Qiu, Y., Cheng, J.C., 2007. Melatonin receptor 1B (MTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis. Spine 32, 1748–1753 (Phila Pa 1976). Reppert, S.M., Godson, C., Mahle, C.D., Weaver, D.R., Slaugenhaupt, S.A., Gusella, J.F., 1995. Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. Proceedings of the National Academy of Sciences of the United States of America 92, 8734–8738. Sumaya, I.C., Masana, M.I., Dubocovich, M.I., 2005. The antidepressant-like effect of the melatonin receptor ligand luzindole in mice during forced swimming requires expression of MT2 but not MT1 melatonin receptors. Journal of Pineal Research 39, 170–177. Wang, L.M., Suthana, N.A., Chaudhury, D., Weaver, D.R., Colwell, C.S., 2005. Melatonin inhibits hippocampal long-term potentiation. Neuroscience 22, 2231–2237. World Health Organization, 1992. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Description and Diagnostic Guidelines. WHO, Geneva. Xiao, C.T., Chu, M.X., Fu, Y., Fang, L., Ye, S.C., 2007. Analysis of polymorphism, structure and function of exon 2 of ovine melatonin receptor 1b gene: a clue as to why it lacks expression in sheep. Journal of Pineal Research 42, 97–104.
Contents lists available at ScienceDirect
Psychiatry Research j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / p s yc h r e s
Brief report
Single nucleotide polymorphisms and mRNA expression for melatonin MT2 receptor in depression Elżbieta Gałecka a, Janusz Szemraj b, Antoni Florkowski c, Piotr Gałecki c, Małgorzata Bieńkiewicz d, Małgorzata Karbownik-Lewińska e,f, Andrzej Lewiński a,f,⁎ a
Department of Endocrinology and Metabolic Diseases, Medical University of Łódź, Poland Department of Medical Biochemistry, Medical University of Łódź, Poland Department of Adult Psychiatry, Medical University of Łódź, Poland d Department of Quality Control and Radiological Protection, Medical University of Łódź, Poland e Department of Oncological Endocrinology, Medical University of Łódź, Poland f Polish Mother's Memorial Hospital, Research Institute, Łódź, Poland b c
a r t i c l e
i n f o
Article history: Received 27 May 2010 Received in revised form 24 January 2011 Accepted 27 January 2011 Keywords: Melatonin MT2 receptor Polymorphism Depression
a b s t r a c t Polymorphisms (rs 4753426 and rs 794837) and expression of the melatonin MT2 receptor gene were evaluated in 181 patients with recurrent depressive disorder (rDD) and 149 healthy subjects of Polish origin. We found an increased risk for rDD in patients with the C allele and a decreased risk in patients with the T allele (rs4753426). Patients with the AT heterozygote (rs794837) had an increased mRNA level. The significance of the MT2 receptor gene and the risk of rDD are suggested. © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Melatonin modulates numerous processes via the MT2 membrane receptor expressed in such brain regions as the suprachiasmatic nucleus (SCN), the cerebellum and the hippocampus (Pandi-Perumal et al., 2008). Activation of the MT2 receptor induces phase-shifts in the electrical activity of SCN neurons and hence results in entrainment of circadian rhythms (Pandi-Perumal et al., 2008). The significance of the MT2 receptor has been demonstrated in neural plasticity (Wang et al., 2005) and neuron protection. The expression of MT2 receptors and their modulatory role were also revealed in cells of the immune system (Lardone et al., 2009). The gene – encoding the MT2 receptor is located at 11q21-22 chromosome (Reppert et al., 1995). For that gene single nucleotide polymorphisms (SNPs), rs4753426 and rs794837, located in the 5′-flanking region, have been described. Both SNPs are in the promoter region. In addition, the rs4753426 SNP located in the regulatory region and the DNA sequence around this site possibly constitute a binding site for one of the transcription factors (Qiu et al., 2007). We studied the relationship between the gene for MT2 receptor polymorphisms and/or gene expression (transcript level), and the risk of recurrent depressive disorder (rDD) risk.
2. Methods 2.1. Subjects A group of 181 patients (102 females—56.4%; mean age 42.6 ± 8.2 years), treated for rDD in the Department of Adult Psychiatry (Medical University of Lodz, Central Poland) meeting the ICD-10 criteria (F33.0–F33.8) (World Health Organization, 1992) and 149 healthy subjects (83 females—55.7%; mean age 38.7 ± 6.7 years) were enrolled into the study. No significant differences were found between the analyzed groups with respect to either age (P N 0.05) or gender (P N 0.05) (Supplementary material). An informed consent was obtained from all the participants of the study. The study protocol was approved by the Local Bioethics Committee No. RNN/626/09/KB.
2.2. Statistical analysis The results are reported as percentages (%) or means with standard deviations (±S.D.). To examine the association between the genotype distribution and rDD, χ2 test—genotypic model was used. Post-hoc power analysis was performed with the use of non-central χ2 distribution. The analysis of association was based on the 95% confidence interval (CI) for the disease odds ratio (ORdis), calculated with the use of a logistic regression model including sex and age as covariates. MT2 gene expression levels were compared by appropriate nonparametric tests: Mann–Whitney's or Kruskal-Wallis. For all the analyses Statistica 8.0 was used and, P ≤0.05 was accepted as the level of statistical significance.
2.3. Procedures ⁎ Corresponding author at: Department of Endocrinology and Metabolic Diseases, Medical University of Łódź, Poland, 281/289, Rzgowska St., PL 93–338 Łódź, Poland. Tel.: +48 42 2711705; fax: +48 42 2711343. E-mail address: [email protected] (A. Lewiński). 0165-1781/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2011.01.021
The genotyping was performed using 0.1 μg of genomic DNA and specific primers for rs4753426 and rs794837 SNPs. The amplification products were digested with restriction enzymes Hae III, Eco NI (New England, BioLabs) respectively and separated on polyacrylamide gel.
E. Gałecka et al. / Psychiatry Research 189 (2011) 472–474 We evaluated a few housekeeping genes from different abundance and functional classes like the beta-actin, GAPDH, HPRT and 18S rRNA genes as endogenous controls. We rejected the beta-actin, GAPDH and HPRT genes because of the existence of corresponding retropseudogenes. The gene for the MT2 receptor and 18S rRNA gene expression was quantified by real-time PCR, using an ABI Prism 7000 Sequence Detection System (Applied Biosystems, Foster City, CA, USA), according to the manufacturer's protocol. Relative gene expression level was normalized to a normal blood sample (calibrator) and was obtained using the ΔΔCt method. Amplification – specific transcripts were further confirmed by melting curve profiles.
3. Results Distribution of genotype frequencies and the Hardy–Weinberg equilibrium in rDD patients and controls were in the following correlation; rs4753425: rDD—χ2 =2.26; controls—χ2 =3.58; rs794837: recurrent DD—χ2 =0.0001; controls—χ2 =3.197. Data and statistical analyses regarding genotype distribution, allele frequency and ORdis values, with age and sex as covariates determined with respect to the rs4753426 and rs794837 SNPs of the MT2 gene are presented in Table 1. Analysis of allele frequency with the use of logistic regression demonstrated that the presence of the C (rs4753426) allele increased rDD risk, whereas the presence of the T (rs4753426) allele decreased the risk in question. Both in the group of patients and in controls, the level of mRNA transcript was significantly different, depending on the genotype (for both examined SNPs, Kruskal-Wallis' test, P b 0.0001). Patients with the AT heterozygote (rs794837) compared with controls had an increased mRNA level (Table 1). No significant differences in the mRNA expression for particular alleles between rDD patients and healthy subjects (rs4753426, P = 0.93 and rs794837, P = 0.17, respectively) were found: 0.063 ± 0.008 (rDD; n = 181) vs 0.061 ± 0.007 (controls; n = 149).
473
Our results are partially supported by earlier findings. Chromosome 11 – at which the gene for the MT2 receptor is mapped – should be of interest in investigations of the gene(s) that are likely to participate in the etiology of depression (Kolomietz et al., 2006). Our results are in line with antidepressant properties of the MT2 receptor antagonist (Sumaya et al., 2005), due to the fact that receptors are expressed in the hippocampus (Musshoff et al., 2002) and participate in the reduction of synaptic plasticity and cell excitability (Hogan et al., 2001). There are also data from animal studies indicating that genetic variants within the MT2 receptor gene may determine its expression (Xiao et al., 2007). Investigated SNPs are located in the promoter region and are in linkage disequilibrium (LD), but we have found that only rs 794837 is related to mRNA expression but rs 4753426 determines the risk of depression. Such results suggest the possibility of these variants being in linkage disequilibrium with other locus conferring susceptibility to depression. An association with the MT2 receptor gene polymorphism was discovered in patients with rheumatoid arthritis (RA) (Ha et al., 2005). Such results may suggest that inflammation and depression have common genes. A role of the MT2 receptor in the mechanism of memory processes and neuronal plasticity as well as its contribution to sleep disorders and neuroprotection was also reported (Larson et al., 2006; Pandi-Perumal et al., 2008). In drawing conclusions from the study, we may cautiously suggest that the MT2 receptor gene may play a role in determining the risk for rDD with a possible unfavorable role of the AT heterozygote in the rs794837 polymorphism. Concerning the rs 4753426 SNP, the C allele may constitute a risk factor, and the T allele is suggested as a protective factor against rDD. Appendix A. Supplementary material Supplementary data to this article can be found online at doi:10.1016/j.psychres.2011.01.021.
4. Discussion To the best of our knowledge, the reported study is the first one investigating SNPs and mRNA expression of the MT2 receptor gene in rDD. Additionally, a gene related to melatonin synthesis (rate-limiting enzyme) was suggested as a susceptibility gene for rDD (Gałecki et al., 2010). We demonstrated that the genetic variants influence the risk for rDD. The obtained data may also indicate that a possible increase of mRNA for the MT2 receptor gene could be, considering some loci, genotype – dependent.
References Gałecki, P., Szemraj, J., Bartosz, G., Bieńkiewicz, M., Gałecka, E., Florkowski, A., Lewiński, A., Karbownik-Lewińska, M., 2010. Single nucleotide polymorphisms and mRNA expression for melatonin synthesis rate limiting enzyme in recurrent depressive disorder. Journal of Pineal Research 48, 311–317. Ha, E., Choe, B.K., Jung, K.H., Yoon, S.H., Park, H.J., Park, H.K., Yim, S.V., Chung, J.H., Bae, H.S., Nam, M., Baik, H.H., Hong, S.J., 2005. Positive relationship between melatonin receptor type 1B polymorphism and rheumatoid factor in rheumatoid arthritis patients in the Korean population. Journal of Pineal Research 39, 201–205.
Table 1 Genotype distribution, allele frequency of MT2 receptor gene polymorphisms (rs4753426 and rs794837), odds ratio of the disease (age and sex adjusted by logistic regression) for both polymorphisms and MT2 receptor mRNA expression regarding rs794837. MT2 receptor rs4753426 Genotype
CC
rDD n; (%) Controls n; (%) Statistical analysis; Post-hoc power analyses
92; (50.83) 81; (44.75) 8; (4.42) 61; (40.94) 75; (50.34) 13; (8.72) 2 χ —4.64; d.f. = 2; P = 0.098; Effect size w = 0.23; n = 330; power 1-β = 99%
CT
TT
−C 265; (73.2) 197; (66.1) ORdis for − C allele: 1.42; (95% CI = 1.01–2.01) ORdis for − T allele: 0.70; (95% CI = 0.50–0.99), P = 0.046
MT2 receptor rs794837 Genotype
AA
AT
TT
rDD n; (%) Controls n; (%) Statistical analysis; Post hoc power analysis
33; (18.23) 102; (56.35) 46; (25.42) 31; (20.81) 74; (49.66) 44; (29.53) 2 χ —1.47; d.f. = 2; P = 0.48; Effect size w = 0.13; n = 330; power 1-β = 76%
−A 168; (46.4) 136; (45.6) ORdis for − A allele: 1.06; (95% CI = 0.77–1.47) ORdis for − T allele: 0.94; (95% CI = 0.68–1.30), P = 0.71
MT2 receptor mRNA expression (rs794837) Genotype
AA
AT
TT
rDD (n) ± S.D. Controls (n) ± S.D.
(33) 0.064 ± 0.007 (31) 0.063 ± 0.007 P N 0.05
(102) 0.065 ± 0.008 (74) 0.062 ± 0.006 P = 0.02
(46) 0.057 ± 0.007 (44) 0.057 ± 0.006 P N 0.05
rDD—patients with recurrent depressive disorder; ORdis—odds ratio of the disease; 95% CI—95% confidence interval, P—level of statistical significance.
474
E. Gałecka et al. / Psychiatry Research 189 (2011) 472–474
Hogan, M.V., El-Sherif, Y., Wieraszko, A., 2001. The modulation of neuronal activity by melatonin: in vitro studies on mouse hippocampal slices. Journal of Pineal Research 30, 87–96. Kolomietz, E., Ben-Omran, T., Chitayat, D., Mah, M., Murphy, J., Nie, G., Teshima, I., 2006. Array-based genomic delineation of a familial duplication 11q14.1-q22.1 associated with recurrent depression. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics 141B, 214–219. Lardone, P.J., Carrillo-Vico, A., Molinero, P., Rubio, A., Guerrero, J.M., 2009. A novel interplay between membrane and nuclear melatonin receptors in human lymphocytes: significance in IL-2 production. Cellular and Molecular Life Sciences: CMLS 66, 516–525. Larson, J., Jessen, R.E., Uz, T., Arslan, A.D., Kurtuncu, M., Imbesi, M., Manev, H., 2006. Impaired hippocampal long-term potentiation in melatonin MT2 receptordeficient mice. Neuroscience Letters 393, 23–26. Musshoff, U., Riewenherm, D., Berger, E., Fauteck, J.D., Speckmann, E.J., 2002. Melatonin receptors in rat hippocampus: molecular and functional investigations. Hippocampus 12, 165–173. Pandi-Perumal, S.R., Trakht, I., Srinivasan, V., Spence, D.W., Maestroni, G.J., Zisapel, N., Cardinali, D.P., 2008. Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Progress in Neurobiology 85, 335–353.
Qiu, X.S., Tang, N.L., Yeung, H.Y., Lee, K.M., Hung, V.W., Ng, B.K., Ma, S.L., Kwok, R.H., Qin, L., Qiu, Y., Cheng, J.C., 2007. Melatonin receptor 1B (MTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis. Spine 32, 1748–1753 (Phila Pa 1976). Reppert, S.M., Godson, C., Mahle, C.D., Weaver, D.R., Slaugenhaupt, S.A., Gusella, J.F., 1995. Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. Proceedings of the National Academy of Sciences of the United States of America 92, 8734–8738. Sumaya, I.C., Masana, M.I., Dubocovich, M.I., 2005. The antidepressant-like effect of the melatonin receptor ligand luzindole in mice during forced swimming requires expression of MT2 but not MT1 melatonin receptors. Journal of Pineal Research 39, 170–177. Wang, L.M., Suthana, N.A., Chaudhury, D., Weaver, D.R., Colwell, C.S., 2005. Melatonin inhibits hippocampal long-term potentiation. Neuroscience 22, 2231–2237. World Health Organization, 1992. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Description and Diagnostic Guidelines. WHO, Geneva. Xiao, C.T., Chu, M.X., Fu, Y., Fang, L., Ye, S.C., 2007. Analysis of polymorphism, structure and function of exon 2 of ovine melatonin receptor 1b gene: a clue as to why it lacks expression in sheep. Journal of Pineal Research 42, 97–104.