Rs6295

Infobox Single nucleotide polymorphism
rsid = 6295
name_1 = C-1019G
name_2 = C(-1019)G
gene = HTR1A
chromosome = 5
region = Promotor
personalitystudy_inventory_1 = NEO PI-R
personalitystudy_trait_1 = Neuroticism
personalitystudy_pmid_1 = 14666415
personalitystudy_genotype_1 = G
personalitystudy_inventory_2 = TPQ
personalitystudy_trait_2 = Harm Avoidance
personalitystudy_pmid_2 = 14666415
personalitystudy_genotype_2 = G

rs6295, also called C(-1019)G, is a gene variation—a single nucleotide polymorphism (SNP)— in the HTR1A gene. It is one of the most investigated SNPs of its gene.Cite journal
author = Antonio Drago, Diana De Ronchi and Alessandro Serretti
title = 5-HT_1A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies
journal = International Journal of Neuropsychopharmacology
pages = 1–21
year = 2007
doi = 10.1017/S1461145707008218] The C-allele is the most prevalent with 0.675 against the G-allele with 0.325 among Caucasian.

The effect of the SNP on the binding potential of the human 5-HT_1A neuroreceptor has been assessed with positron emission tomography and the WAY-100635 radioligand, with a study reporting no apparent influence from the SNP.Cite journal
author = Sean P. David, Naga Venkatesha Murthy, Eugenii A. Rabiner, Marcus R. Munafó, Elaine C. Johnstone, Robyn Jacob, Robert T. Walton & Paul M. Grasby
title = A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans
journal = The Journal of Neuroscience
year = 2005
month = March
volume = 25
issue = 10
pages = 2586–2590
url = http://www.jneurosci.org/cgi/content/full/25/10/2586
pmid = 15758168
doi = 10.1523/JNEUROSCI.3769-04.2005]

Disorders

The SNP has been investigated for association with suicide attempts,Cite journal
author = Sylvie Lemonde, Gustavo Turecki, David Bakish, Lisheng Du, Pavel D. Hrdina, Christopher D. Bown, Adolfo Sequeira, Neena Kushwaha, Stephen J. Morris, Ajoy Basak, Xiao-Ming Ou, and Paul R. Albert
title = Impaired Repression at a 5-Hydroxytryptamine 1A Receptor Gene Polymorphism Associated with Major Depression and Suicide
journal = The Journal of Neuroscience
month = September
year = 2003
volume = 23
issue = 25
pages = 8788–8799
url = http://www.jneurosci.org/cgi/content/full/23/25/8788] [Cite journal
author = Danuta Wasserman, Thomas Geijer, Marcus Sokolowski, Vsevolod Rozanov and Jerzy Wasserman
title = The serotonin 1A receptor C(-1019)G polymorphism in relation to suicide attempt
journal = Behavioral and Brain Functions
year = 2006
volume = 2
pages =14
url = http://www.behavioralandbrainfunctions.com/content/2/1/14
doi = 10.1186/1744-9081-2-14] and psychiatric disorders. [Cite journal
author = Antonio Drago, Diana De Ronchi and Alessandro Serretti
title = 5-HT_1A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies
journal = Internal Journal of Neuropsychopharmacology
year = 2007
page = 1–21
pmid = 18047755] One study found an association of the variant with schizophrenia. [Cite journal
author = Yung-yu Huang, Cristina Battistuzzi, Maria A. Oquendo, Jill Harkavy-Friedman, Laurence Greenhill, Gil Zalsman, Beth Brodsky, Victoria Arango, David A. Brent and J. John Mann
title = Human 5-HT1A receptor C(−1019)G polymorphism and psychopathology
journal = The International Journal of Neuropsychopharmacology
year = 2004
volume = 7
pages = 441–451
doi = 10.1017/S1461145704004663
pmid = 15469667] Some studies associate the G-allele or GG-genotype with depression. [Cite journal
author = Ramin V. Parsey, Maria A. Oquendo, R. Todd Ogden, Doreen M. Olvet, Norman Simpson, Yung-Yu Huang, Ronald L. Van Heertum, Victoria Arango & J. John Mann
title = Altered serotonin 1A binding in major depression: a carbonyl-C-11WAY100635 positron emission tomography study
journal = Biological Psychiatry
volume = 59
issue = 2
pages = 106–103
year = 2006
month = January
doi = 10.1016/j.biopsych.2005.06.016
pmid = 16154547] Not all studies show associations between the disorder and the G-allele. In one study of premenstrual dysphoric disorder C/C was found as the high-risk genotype. [Cite journal
author = Vandana Dhingra, Julia L. Magnay, P. M. Shaughn O'Brien, FRCOG1, Gail Chapman, MPhil, Anthony A. Fryer and Khaled M. K. Ismail
title = Serotonin Receptor 1A C(-1019)G Polymorphism Associated With Premenstrual Dysphoric Disorder
journal = Obstetrics & Gynecology
year = 2007
volume = 110
pages = 788–792
url = http://www.greenjournal.org/cgi/content/abstract/110/4/788]

Several studies have examine the SNP association with medical treatment response, e.g., antidepressant response in mood disorders, e.g., one study reported worse response for G-allele patients. [Cite journal
author = Alessandro Serretti et al.
title = The C(–1019)G polymorphism of the 5-HT1A gene promotor and antidepressant response in mood disorders: preliminary findings
journal = International Journal of Neuropsychophamarcology
volume = 7
pages = 453–460
year = 2004
doi = 10.1017/S1461145704004687]

Personality

The polymorphism has also been investigated for links to personality traits:Persons with the G-allele of the polymorphism may have higher personality score for the NEO PI-R Neuroticism and TPQ Harm Avoidance traits. [Cite journal
author = A. Strobel, L. Gutknecht, C. Rothe, A. Reif, R. Mössner, Y. Zeng, B. Brocke1 and Klaus-Peter Lesch
title = Allelic variation in 5-HT 1A receptor expression is associated with anxiety- and depression-related personality traits
journal = Journal of Neural Transmission
volume = 110
issue = 12
pages = 1445–1453
month = December
year = 2003
doi = 10.1007/s00702-003-0072-0
url = http://www.springerlink.com/content/cv9169brffg67yld/] However, not all studies can find a clear association. [Cite journal
author = G. Koller, B. Bondy, U. W. Preuss, P. Zill & M. Soyka
title = The C(-1019)G 5-HT1A promoter polymorphism and personality traits: no evidence for significant association in alcoholic patients
journal =
volume = 2
pages = 7
year = 2006
month =
doi = 10.1186/1744-9081-2-7
pmid = 16504134] One study has studied another trait and found higher score on Temperament and Character Inventory self-transcendence scale for G-allele subjects among mood disorder patients. [Cite journal
author = Cristina Lorenzi, Alessandro Serretti, Laura Mandelli, Viviana Tubazio, Cristina Ploia, Enrico Smeraldi
title = 5-HT_1A polymorphism and self-transcendence in mood disorders
journal =
volume = 137B
issue = 1
pages 33–35
doi = 10.1002/ajmg.b.30111]

Other SNPs

There are a number of other SNPs for the HTR1A gene: C549T, Ile28Val (rs1799921), Pro16Leu (rs1800041), Gly272Asp (rs1800042) and
G294A (rs6294). [Cite web
title = Meta-Analysis of All Published Schizophrenia-Association Studies (Case-Control Only) HTR1A_C1019G
url = http://www.schizophreniaforum.org/res/sczgene/meta.asp?geneID=335
publisher = Schizophrenia Research Forum
accessdate = 2008-06-18]

References