NR3C1 Polymorphisms for Genetic Susceptibility to Schizophrenia
0
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Objectives : Psychological stress has been known to increase the risk of schizophrenia. Because stress responses are mainly mediated by cortisol, the action of the glucocorticoid receptors (Nuclear Receptor Subfamily 3 Group C Member 1, NR3C1) is possibly related to the pathogenesis of schizophrenia. In this study, we investigated the associations between polymorphisms of NR3C1 and schizophrenia. Methods : Four single nucleotide polymorphisms (SNPs) (rs17100236, rs2963155, rs9324924, and rs7701443) of NR3C1 were genotyped in 208 patients with schizophrenia and 339 healthy individuals. A chi-square test was performed to test differences in allele distributions among groups. A multiple logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), and multiple inheritance models to analyze the associations between schizophrenia and SNPs (the dominant, recessive and additive models). Results : The minor allele frequencies of two SNPs were significantly higher in the schizophrenia group than in those of the control group (rs2963155 G > A : 0.25 vs. 0.18, p = 0.0066 ; rs7701443 A > G : 0.40 vs. 0.33, p = 0.012). The genotype frequencies of two SNPs were found to be significantly different between patients with schizophrenia and controls in the dominant model (rs2963155 : AG/GG vs. AA, OR = 1.66, 95% CI = 1.16-2.38, p = 0.0055, rs7701443 : AG/AA vs. GG, OR = 1.61, 95% CI = 1.11-2.34, p = 0.01) and the log-additive model (rs2963155 : AG vs. GG vs. AA, OR = 1.54, 95% CI = 1.13-2.10, p = 0.0067). Conclusions : This study showed significant associations between NR3C1 polymorphisms and schizophrenia. It suggests that NR3C1 may play a role in the pathogenesis of schizophrenia.
Abstract
Objectives : Psychological stress has been known to increase the risk of schizophrenia. Because stress responses are mainly mediated by cortisol, the action of the glucocorticoid receptors (Nuclear Receptor Subfamily 3 Group C Member 1, NR3C1) is possibly related to the pathogenesis of schizophrenia. In this study, we investigated the associations between polymorphisms of NR3C1 and schizophrenia. Methods : Four single nucleotide polymorphisms (SNPs) (rs17100236, rs2963155, rs9324924, and rs7701443) of NR3C1 were genotyped in 208 patients with schizophrenia and 339 healthy individuals. A chi-square test was performed to test differences in allele distributions among groups. A multiple logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), and multiple inheritance models to analyze the associations between schizophrenia and SNPs (the dominant, recessive and additive models). Results : The minor allele frequencies of two SNPs were significantly higher in the schizophrenia group than in those of the control group (rs2963155 G > A : 0.25 vs. 0.18, p = 0.0066 ; rs7701443 A > G : 0.40 vs. 0.33, p = 0.012). The genotype frequencies of two SNPs were found to be significantly different between patients with schizophrenia and controls in the dominant model (rs2963155 : AG/GG vs. AA, OR = 1.66, 95% CI = 1.16-2.38, p = 0.0055, rs7701443 : AG/AA vs. GG, OR = 1.61, 95% CI = 1.11-2.34, p = 0.01) and the log-additive model (rs2963155 : AG vs. GG vs. AA, OR = 1.54, 95% CI = 1.13-2.10, p = 0.0067). Conclusions : This study showed significant associations between NR3C1 polymorphisms and schizophrenia. It suggests that NR3C1 may play a role in the pathogenesis of schizophrenia.
참고문헌 (40)
- Corcoran C, "The stress cascade and schizophrenia : etiology and onset", Schizophr Bull, 29, pp.671~692 (2003)
- Norman RM, "Stressful life events and schizophrenia. I: a review of the research", Br J Psychiatry, 162, pp.161~166 (1993)
- Myin-Germeys I, "Emotional reactivity to daily life stress in psychosis", Arch Gen Psychiatry, 58, pp.1137~1144 (2001)
- Green MJ, "Stress, schizophrenia and bipolar disorder", Curr Top Behav Neurosci, 18, pp.217~235 (2014)
- Cotter D, "Stress and the progression of the developmental hypothesis of schizophrenia", Br J Psychiatry, 181, pp.363~365 (2002)
- Mondelli V, "Abnormal cortisol levels during the day and cortisol awakening response in first-episode psychosis : the role of stress and of antipsychotic treatment", Schizophr Res, 116, pp.234~242 (2010)
- Lammers CH, "Combined dexamethasone", corticotropinreleasing hormone test in patients with schizophrenia and in normal controls : II, 1995, pp.38, 803~807
- Gallagher P, "Plasma cortisol-dehydroepiandrosterone(DHEA)ratios in schizophrenia and bipolar disorder", Schizophr Res, 90, pp.258~265 (2007)
- Venkatasubramanian G, "Effect of antipsychotic treatment on Insulin-like growth factor-1 and cortisol in schizophrenia : a longitudinal study", Schizophr Res, 119, pp.131~137 (2010)
- Garner B, "Cortisol and dehydroepiandrosterone-sulphate levels correlate with symptom severity in first-episode psychosis", J Psychiatr Res, 45, pp.249~255 (2011)
- Webster MJ, "Regional specificity of brain glucocorticoid receptor mRNA alterations in subjects with schizophrenia and mood disorders", Mol Psychiatry, 7, pp.985~994 (2002)
- Sinclair D, "Glucocorticoid receptor 1B and 1C mRNA transcript alterations in schizophrenia and bipolar disorder, and their possible regulation by GR gene variants", PLoS One, 7, pp.e31720~ (2012)
- Oakley RH, "The biology of the glucocorticoid receptor : new signaling mechanisms in health and disease", J Allergy Clin Immunol, 132, pp.1033~1044 (2013)
- Rhen T, "Antiinflammatory action of glucocorticoids--new mechanisms for old drugs", N Engl J Med, 353, pp.1711~1723 (2005)
- Bray PJ, "Variations of the human glucocorticoid receptor gene(NR3C1) : pathological and in vitro mutations and polymorphisms", Hum Mutat, 21, pp.557~568 (2003)
- Pimm J, "The Epsin 4 gene on chromosome 5q, which encodes the clathrin-associated protein enthoprotin, is involved in the genetic susceptibility to schizophrenia", Am J Hum Genet, 76, pp.902~907 (2005)
- Petryshen TL, "Genetic investigation of chromosome 5q GABAA receptor subunit genes in schizophrenia", Mol Psychiatry, 10, pp.1074~1088 (2005)
- Paunio T, "Genome-wide scan in a nationwide study sample of schizophrenia families in Finland reveals susceptibility loci on chromosomes 2q and 5q", Hum Mol Genet, 10, pp.3037~3048 (2001)
- Sklar P, "Genome-wide scan in Portuguese Island families identifies 5q31-5q35 as a susceptibility locus for schizophrenia and psychosis", Mol Psychiatry, 9, pp.213~218 (2004)
- Gabriel SB, "The structure of haplotype blocks in the human genome", Science, 296, pp.2225~2229 (2002)
- Perroud N, "Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma", Transl Psychiatry, 1, pp.e59~ (2011)
- Klengel T, "The role of DNA methylation in stress-related psychiatric disorders", Neuropharmacology, 80, pp.115~132 (2014)
- van Rossum EF, "Polymorphisms of the glucocorticoid receptor gene and major depression", Biol Psychiatry, 59, pp.681~688 (2006)
- Gałecka E, "Single nucleotide polymorphisms of NR3C1gene and recurrent depressive disorder in population of Poland", Mol Biol Rep, 40, pp.1693~1699 (2013)
- Lahti J, "Glucocorticoid receptor gene haplotype predicts increased risk of hospital admission for depressive disorders in the Helsinki birth cohort study", J Psychiatr Res, 45, pp.1160~1164 (2011)
- Szczepankiewicz A, "Glucocorticoid receptor polymorphism is associated with major depression and predominance of depression in the course of bipolar disorder", J Affect Disord, 134, pp.138~144 (2011)
- Spijker AT, "Functional polymorphism of the glucocorticoid receptor gene associates with mania and hypomania in bipolar disorder", Bipolar Disord, 11, pp.95~101 (2009)
- Manenschijn L, "Glucocorticoid receptor haplotype is associated with a decreased risk of delirium in the elderly", Am J Med Genet B Neuropsychiatr Genet, 156B, pp.316~321 (2011)
- Desrivières S, "Glucocorticoid receptor(NR3C1)gene polymorphisms and onset of alcohol abuse in adolescents", Addict Biol, 16, pp.510~513 (2011)
- Feng J, "Five missense variants in the amino-terminal domain of the glucocorticoid receptor : no association with puerperal psychosis or schizophrenia", Am J Med Genet, 96, pp.412~417 (2000)
- Krupoves A, "Variation in the glucocorticoid receptor gene(NR3C1)may be associated with corticosteroid dependency and resistance in children with Crohn’s disease", Pharmacogenet Genomics, 21, pp.454~460 (2011)
- Yang G, "NR3C1 gene polymorphism for genetic susceptibility to infantile spasms in a Chinese population", Life Sci, 91, pp.37~43 (2012)
- Yan YX, "Associations between polymorphisms in the glucocorticoid-receptor gene and cardiovascular risk factors in a Chinese population", J Epidemiol, 23, pp.389~395 (2013)
- Chen YF, "Association of glucocorticoid receptor gene polymorphisms with systemic lupus erythematosus in a Chinese population", Int J Rheum Dis, 20, pp.2053~2061 (2017)
- Xue L, "Single nucleotide polymorphisms in non-coding region of the glucocorticoid receptor gene and prednisone response in childhood acute lymphoblastic leukemia", Leuk Lymphoma, 56, pp.1704~1709 (2015)
- Fang SY, "Correlation between polymorphisms of the NR3C1 gene and glucocorticoid effectiveness in patients with pemphigus vulgaris", Sci Rep, 7, pp.11890~ (2017)
- Mizoguchi K, "Endogenous glucocorticoids are essential for maintaining prefrontal cortical cognitive function", J Neurosci, 24, pp.5492~5499 (2004)
- Kumsta R, "Working memory performance is associated with common glucocorticoid receptor gene polymorphisms", Neuropsychobiology, 61, pp.49~56 (2010)
- El-Hage W, "Genetic modulation of neural response during working memory in healthy individuals : interaction of glucocorticoid receptor and dopaminergic genes", Mol Psychiatry, 18, pp.174~182 (2013)
- Van Craenenbroeck K, "Role of glucocorticoids in dopamine-related neuropsychiatric disorders", Mol Cell Endocrinol, 245, pp.10~22 (2005)