{{Rsnum
|rsid=25531
|Gene=SLC6A4
|Chromosome=17
|position=30237328
|Orientation=minus
|GMAF=0.1088
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=SLC6A4
}}According to David Hinds of 23andMe on community forums, "nearly everyone (99.97%) is getting called as CC, and there is no clear heterozygote cluster" ... "the genotype calls for [[rs25531]] on our platform are not meaningful." Looking at OpenSNP frequency data, this seems to be universal for direct to consumer genotyping services at this stage.

The minor allele (G) of [[rs25531]] is almost always in phase with the long (L) allele of the [[5-HTTLPR]], which is the most commonly studied variation in this region. The (L) long allele may be associated with lower levels of serotonin.{{PMID|8929413}}

The article and video from "The Atlantic" suggests that children with the short allele (A), may need and benefit greatly from more maternal support
*http://www.theatlantic.com/doc/200912/dobbs-orchid-gene

In contrast to earlier reports linking [[rs25531]], a SNP in the serotonin transporter [[SLC6A4]] gene, to obsessive compulsive disorder (OCD), a March 2007 publication finds no significant association studying "the largest sample size of OCD patients (N=347) and controls (N=749) ever investigated". {{PMID|17375136}}

A separate study of 75 patients suffering mood disorders after traumatic brain injury (TBI) concluded that there was no evidence of association between [[rs25531]] and depression post-TBI.{{PMID|18465388}}

A small study (62 patients and 62 matched controls) investigated this SNP in relation to [[blushing]]. (Blushing is considered to be one of the prime pathophysiological markers of [[social anxiety disorder]].) The less active [[5-HTTLPR]] genotypes were nominally significantly associated with increased blushing propensity in patients with [[social anxiety disorder]], and association remained significant even when statistically controlled for he influence of depression.{{PMID|18629430}}

A study of 94 depressed patients who attempted suicide compared to 94 without psychiatric disorders found no evidence of an association with [[rs25531]].{{PMID|19103261}}

A study of 97 "normal" individuals concluded that [[rs25531]](G;G) individuals selectively process positive affective material alongside selective avoidance of negative affective material, in a manner absent among individuals carrying a [[rs25531]](A) allele. To put it another way, if this conclusion drawn from a very small sample of people can be replicated, [[rs25531]](G;G) individuals may have a tendency to be optimists and to be more resilient to stress.{{doi|10.1098/rspb.2008.1788}}

A study published in 2011 of 2,500+ individuals followed from 1995 - 2008 as part of the US National Longitudinal Study of Adolescent Health found that twice as many respondents with two 5-HTTLPR long variants said they were very satisfied with life compared with carriers of two short versions. Conversely, 26% of those carrying two short alleles said they were dissatisfied with life, compared with 20% of people carrying two long variants.{{doi|10.1038/jhg.2011.39}} This [http://www.stat.columbia.edu/~cook/movabletype/archives/2011/05/discovered_the.html blog post] investigates the statistics.

A study of 135 patients with major depressive disorder (mean age 31.1+/-11.6 years, 68% females) treated with [[escitalopram]] 10-20 mg/day for 12 weeks concluded that patients carrying the [[rs25531]](A) allele may be at increased risk for side effects (e.g. headaches), but they say no associations with efficacy.{{PMID|19272758}}
{{PMID Auto
|PMID=19487392
|Title=Serotonin Transporter Gene (SLC6A4) Promoter Polymorphisms and the Susceptibility to [[Posttraumatic Stress Disorder]] in the General Population
}}
{{PMID Auto
|PMID=19521089
|Title=Serotonin Transporter Gene Polymorphic Element 5-HTTLPR Increases the Risk of Sporadic Parkinson's Disease in Italy
}}

[http://ibgwww.colorado.edu/genotyping_lab/pdf/5HTTLPR.pdf Protocol] for genotyping rs25531
{{PMID Auto
|PMID=19570226
|Title=Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans
|OA=1
}}
{{PMID Auto
|PMID=19685963
|Title=Association of the serotonin transporter gene promoter region (5-HTTLPR) polymorphism with biased attention for emotional stimuli
|OA=1
}}
{{PMID Auto
|PMID=19806148
|Title=Association of SLC6A4 variants with obsessive-compulsive disorder in a large multicenter US family study
}}
{{PMID Auto
|PMID=19911410
|Title=Do 5HTTLPR and stress interact in risk for depression and suicidality? Item response analyses of a large sample
|OA=1
}}

{{PharmGKB
|RSID=rs25531
|Name_s=
|Gene_s=SLC6A4
|Feature=
|Evidence=PubMed ID:15993855
|Annotation=This vatiant in the SLC6A4 gene, located upstream of the HTTLPR polymorphism, showed evidence of an association with treatment response, and biochemical experiments showed this polymorphism altered binding of nuclear extracts to a consensus sequence for the activator protein 2 transcription factor, which is believed to be a critical factor in regulating neural gene expression in mammals.
|Drugs=
|Drug Classes=ANTIDEPRESSANTS
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA164920378
}}
{{PMID Auto
|PMID=20031235
|Title=Serotonin transporter polymorphisms and early response to antipsychotic treatment in first episode of psychosis
}}
{{PMID Auto
|PMID=20090673
|Title=Serotonin Transporter Genotype and Action Monitoring Dysfunction: A Possible Substrate Underlying Increased Vulnerability to Depression
|OA=1
}}
{{PMID Auto
|PMID=20146650
|Title=Association analysis between gene variants of the tyrosine hydroxylase and the serotonin transporter in borderline personality disorder
}}
{{PMID Auto
|PMID=20175892
|Title=Study of the serotonin transporter (SLC6A4) and BDNF genes in French patients with non syndromic mental deficiency
|OA=1
}}
{{PMID Auto
|PMID=20462563
|Title=Analysis of the serotonin transporter promoter rs25531 polymorphism in premenstrual dysphoric disorder
}}
{{PMID Auto
|PMID=20468059
|Title=No association of the serotonin transporter polymorphisms 5-HTTLPR and RS25531 with schizophrenia or neurocognition
|OA=1
}}
{{PMID Auto
|PMID=20588071
|Title=Norepinephrine and Serotonin Transporter Genes: Impact on Treatment Response in Depression
}}
{{PMID Auto
|PMID=20694965
|Title=Association of the serotonin transporter promoter region polymorphism with biased attention for negative word stimuli
|OA=1
}}
{{PMID Auto
|PMID=20920548
|Title=Lack of association between the 5-HTTLPR and the error-related negativity (ERN)
}}

{{PharmGKB
|RSID=rs25531
|Name_s=
|Gene_s=SLC6A4
|Feature=
|Evidence=PubMed ID:18618621
|Annotation=This promoter SNP is not associated with depression remission frequency upon treatment with citalopram in white Hispanics, white non-Hispanics, or Blacks.
|Drugs=citalopram
|Drug Classes=
|Diseases=Depression
|Curation Level=Curated
|PharmGKB Accession ID=PA162008701
}}
{{PMID Auto
|PMID=21245616
|Title=Association of serotonin transporter gene polymorphisms with obsessive-compulsive disorder (OCD) in a South Indian population
|OA=1
}}

{{PMID Auto
|PMID=21319930
|Title=Associations between serotonin transporter gene promoter region (5-HTTLPR) polymorphism and gaze bias for emotional information
}}

{{PMID Auto
|PMID=21105279
|Title=Relation of serotonin transporter genetic variation to efficacy of escitalopram for generalized anxiety disorder in older adults
|OA=1
}}
{{PMID Auto
|PMID=21504541
|Title=ASSOCIATION BETWEEN NEONATAL TEMPERAMENT, SLC6A4, DRD4 AND A FUNCTIONAL POLYMORPHISM LOCATED IN TFAP2B
}}

{{PMID Auto
|PMID=21660253
|Title=A novel study and meta-analysis of the genetic variation of the serotonin transporter promoter in the italian population do not support a large effect on Alzheimer's disease risk
|OA=1
}}

{{PMID Auto
|PMID=21658141
|Title=Genetic variants in the serotonin transporter influence the efficacy of bupropion and nortriptyline in smoking cessation
}}

{{PMID Auto
|PMID=21423614
|Title=Perception of thermal pain and the thermal grill illusion is associated with polymorphisms in the serotonin transporter gene
|OA=1
}}

{{PMID Auto
|PMID=22086748
|Title=The Serotonin Transporter Promoter Polymorphism (5-HTTLPR) Affects the Relation between Antidepressant Serum Concentrations and Effectiveness in Major Depression
}}

{{PMID Auto
|PMID=22271509
|Title=Association between the serotonin transporter triallelic genotype and eating problems is moderated by the experience of childhood trauma in women
|OA=1
}}

{{PMID Auto
|PMID=21364197
|Title=Effects of 5HTTLPR on cardiovascular response to an emotional stressor
|OA=1
}}

{{PMID Auto
|PMID=21681867
|Title=Serotonin transporter gene and childhood trauma--a G × E effect on anxiety sensitivity
}}

{{PMID Auto
|PMID=22590463
|Title=Influence of threat and serotonin transporter genotype on interference effects
|OA=1
}}
{{PMID Auto
|PMID=16402131
|Title=Simultaneous genotyping of four functional loci of human SLC6A4, with a reappraisal of 5-HTTLPR and rs25531.
}}

{{PMID Auto
|PMID=17284168
|Title=Serotonergic genes modulate amygdala activity in major depression.
}}

{{PMID Auto
|PMID=18050262
|Title=Serotonin transporter polymorphism (5-HTTLPR) association with melancholic depression: a female specific effect?
}}

{{PMID Auto
|PMID=18441666
|Title=Extended evaluation of serotonin transporter gene functional polymorphisms in subjects with post-stroke depression.
}}

{{PMID Auto
|PMID=18444253
|Title=Additional functional variation at the SLC6A4 gene.
|OA=1
}}

{{PMID Auto
|PMID=18661222
|Title=5-HTTLPR and gender moderate changes in negative affect responses to tryptophan infusion.
|OA=1
}}

{{PMID Auto
|PMID=18824000
|Title=How the serotonin story is being rewritten by new gene-based discoveries principally related to SLC6A4, the serotonin transporter gene, which functions to influence all cellular serotonin systems.
|OA=1
}}

{{PMID Auto
|PMID=18951433
|Title=Lack of association of the serotonin transporter gene promoter region polymorphism, 5-HTTLPR, including rs25531 with cigarette smoking and alcohol consumption.
}}

{{PMID Auto
|PMID=18981341
|Title=Association of serotonin transporter gene polymorphisms with poststroke depression.
|OA=1
}}

{{PMID Auto
|PMID=19015103
|Title=Oxytocin receptor (OXTR) and serotonin transporter (5-HTT) genes associated with observed parenting.
|OA=1
}}

{{PMID Auto
|PMID=19020798
|Title=Association study to evaluate the serotonin transporter and apolipoprotein E genes in frontotemporal lobar degeneration in Italy.
}}

{{PMID Auto
|PMID=19032574
|Title=Characterization of a functional polymorphism in the 3' UTR of SLC6A4 and its association with drinking intensity.
|OA=1
}}

{{PMID Auto
|PMID=19122845
|Title=An examination of the association between the 5-HTT promoter region polymorphism and depressogenic attributional styles in childhood.
|OA=1
}}

{{PMID Auto
|PMID=19125330
|Title=The serotonin transporter polymorphism rs25531 is associated with irritable bowel syndrome.
|OA=1
}}

{{PMID Auto
|PMID=19249159
|Title=Sex-specific association between the 5-HTT gene-linked polymorphic region and basal cortisol secretion.
}}

{{PMID Auto
|PMID=19429111
|Title=No association between polymorphism of serotonin transporter gene and depression in Parkinson's disease in Chinese.
}}

{{PMID Auto
|PMID=19541292
|Title=Accurate, Large-Scale Genotyping of 5HTTLPR and Flanking Single Nucleotide Polymorphisms in an Association Study of Depression, Anxiety, and Personality Measures.
|OA=1
}}

{{PMID Auto
|PMID=19625753
|Title=The serotonin transporter promoter polymorphic region is not a risk factor for Alzheimer's disease related behavioral disturbances.
}}

{{PMID Auto
|PMID=19742166
|Title=Epistasis between IL1A, IL1B, TNF, HTR2A, 5-HTTLPR and TPH2 variations does not impact alcohol dependence disorder features.
|OA=1
}}

{{PMID Auto
|PMID=19860858
|Title=Combinatorial interaction between two human serotonin transporter gene variable number tandem repeats and their regulation by CTCF.
|OA=1
}}

{{PMID Auto
|PMID=19884608
|Title=Interactive effect of stressful life events and the serotonin transporter 5-HTTLPR genotype on posttraumatic stress disorder diagnosis in 2 independent populations.
|OA=1
}}

{{PMID Auto
|PMID=19962442
|Title=Emotion specific modulation of automatic amygdala responses by 5-HTTLPR genotype.
}}

{{PMID Auto
|PMID=19996755
|Title=Serotonin transporter triallelic genotype and response to citalopram and risperidone in dementia with behavioral symptoms.
|OA=1
}}

{{PMID Auto
|PMID=20406689
|Title=Serotonin transporter polymorphisms (SLC6A4 insertion/deletion and rs25531) do not affect the availability of 5-HTT to [11C] DASB binding in the living human brain.
}}

{{PMID Auto
|PMID=20450949
|Title=Serotonin transporter gene polymorphisms and treatment-resistant depression.
}}

{{PMID Auto
|PMID=20452607
|Title=Influence of serotonin transporter gene polymorphisms on clozapine response in Brazilian schizophrenics.
}}

{{PMID Auto
|PMID=20452754
|Title=Mixture regression analysis on age at onset in bipolar disorder patients: investigation of the role of serotonergic genes.
}}

{{PMID Auto
|PMID=20455953
|Title=Serotonin transporter gene, childhood emotional abuse and cognitive vulnerability to depression.
|OA=1
}}

{{PMID Auto
|PMID=20505557
|Title=Haplotypes of dopamine and serotonin transporter genes are associated with antisocial personality disorder in alcoholics.
}}

{{PMID Auto
|PMID=20515362
|Title=Genetic predictors of response to treatment with citalopram in depression secondary to traumatic brain injury.
|OA=1
}}

{{PMID Auto
|PMID=20584552
|Title=The role of clinical variables, neuropsychological performance and SLC6A4 and COMT gene polymorphisms on the prediction of early response to fluoxetine in major depressive disorder.
}}

{{PMID Auto
|PMID=20862697
|Title=Rare genotype combination of the serotonin transporter gene associated with treatment response in severe personality disorder.
}}

{{PMID Auto
|PMID=20971165
|Title=Relationships among 5-HTT genotype, life events and gender in the recognition of facial emotions.
}}

{{PMID Auto
|PMID=21166770
|Title=Dopamine D4 receptor and serotonin transporter gene effects on the longitudinal development of infant temperament.
|OA=1
}}

{{PMID Auto
|PMID=21172166
|Title=Pharmacogenetics of antidepressant response.
|OA=1
}}

{{PMID Auto
|PMID=21232011
|Title=Serotonin transporter allelic variation in mothers predicts maternal sensitivity, behavior and attitudes toward 6-month-old infants.
}}

{{PMID Auto
|PMID=21290142
|Title=Parent of origin effect and allelic expression imbalance of the serotonin transporter in bipolar disorder and suicidal behaviour.
}}

{{PMID Auto
|PMID=21356267
|Title=5-HTTLPR and COMTval158met genotype gate amygdala reactivity and habituation.
}}

{{PMID Auto
|PMID=21429092
|Title=Serotonin transporter gene variants and prediction of stress-induced risk for psychological distress.
}}

{{PMID Auto
|PMID=21441157
|Title=Serotonin transporter gene polymorphism in Chinese patients with poststroke depression: a case-control study.
}}

{{PMID Auto
|PMID=21453464
|Title=The influence of psychiatric screening in healthy populations selection: a new study and meta-analysis of functional 5-HTTLPR and rs25531 polymorphisms and anxiety-related personality traits.
|OA=1
}}

{{PMID Auto
|PMID=21497794
|Title=A functional variant of the serotonin transporter gene (SLC6A4) moderates impulsive choice in attention-deficit/hyperactivity disorder boys and siblings.
|OA=1
}}

{{PMID Auto
|PMID=21818827
|Title=The relationship between combat-related posttraumatic stress disorder and the 5-HTTLPR/rs25531 polymorphism.
|OA=1
}}

{{PMID Auto
|PMID=21893641
|Title=Acute and posttraumatic stress symptoms in a prospective gene x environment study of a university campus shooting.
|OA=1
}}

{{PMID Auto
|PMID=22094432
|Title=Perception of a naturalistic stressor interacts with 5-HTTLPR/rs25531 genotype and gender to impact reward responsiveness.
|OA=1
}}

{{PMID Auto
|PMID=22348680
|Title=Somatic markers mediate the effect of serotonin transporter gene polymorphisms on Iowa Gambling Task.
}}

{{PMID Auto
|PMID=22489680
|Title=No difference in 5-HTTLPR and Stin2 polymorphisms frequency between premature ejaculation patients and controls.
}}

{{PMID Auto
|PMID=22520017
|Title=Suicide ideators and attempters with schizophrenia--the role of 5-HTTLPR, rs25531, and 5-HTT VNTR Intron 2 variants.
}}

{{PMID Auto
|PMID=23236014
|Title=Polymorphisms of the serotonin transporter gene and post-stroke depression: a meta-analysis
}}

{{PMID Auto
|PMID=23288236
|Title=5-HTTLPR rs25531A &gt; G differentially influence paroxetine and fluvoxamine antidepressant efficacy: a randomized, controlled trial
}}

{{PMID Auto
|PMID=23787408
|Title=Prediction of the time-course pattern of remission in depression by using clinical, neuropsychological, and genetic variables
}}

{{PMID Auto
|PMID=23021380
|Title=Strong effects of environmental factors on prevalence and course of major depressive disorder are not moderated by 5-HTTLPR polymorphisms in a large Dutch sample
}}

{{PMID Auto
|PMID=23499791
|Title=Resting-state cerebral blood flow in amygdala is modulated by sex and serotonin transporter genotype
}}

{{PMID Auto
|PMID=22390669
|Title=Interaction between serotonin transporter polymorphism (5-HTTLPR) and stressful life events in adolescents' trajectories of anxious/depressed symptoms.
|OA=1
}}

{{PMID Auto
|PMID=22623017
|Title=Serotonin transporter-linked polymorphic region (5-HTTLPR) genotype is associated with cortisol responsivity to naloxone challenge.
}}

{{PMID Auto
|PMID=22836288
|Title=5-HTTLPR X stress in adolescent depression: moderation by MAOA and gender.
}}

{{PMID Auto
|PMID=22884012
|Title=Influence of serotonin transporter promoter variation on the effects of separation from parent/partner on depression.
}}

{{PMID Auto
|PMID=22907732
|Title=Interaction between polymorphisms in serotonin transporter (SLC6A4) and serotonin receptor 2A (HTR2A) genes predict treatment response to venlafaxine XR in generalized anxiety disorder.
}}

{{PMID Auto
|PMID=22913298
|Title=Respiratory sinus arrhythmia and serotonin transporter promoter gene polymorphisms: taking a triallelic approach makes a difference.
}}

{{PMID Auto
|PMID=22921508
|Title=Association between serotonin transporter promoter polymorphisms and psychological distress in a diabetic population.
}}

{{PMID Auto
|PMID=23033208
|Title=Characterization of serotonin transporter gene (SLC6A4) polymorphisms and its association with drug dependence in a Jordanian Arab population.
}}

{{PMID Auto
|PMID=23101739
|Title=The Generation R Study: A review of design, findings to date, and a study of the 5-HTTLPR by environmental interaction from fetal life onward.
}}

{{PMID Auto
|PMID=23123360
|Title=Allele-specific associations of 5-HTTLPR/rs25531 with ADHD and autism spectrum disorder.
|OA=1
}}

{{PMID Auto
|PMID=23149035
|Title=Association study of serotonin transporter availability and SLC6A4 gene polymorphisms in patients with major depression.
}}

{{PMID Auto
|PMID=23261136
|Title=State dependent gene-environment interaction: serotonin transporter gene-child abuse interaction associated with suicide attempt history among depressed psychiatric inpatients.
}}

{{PMID Auto
|PMID=23277270
|Title=5-HTTLPR rs25531A > G Differentially Influence Paroxetine and Fluvoxamine Antidepressant Efficacy: A Randomized Controlled Trial.
}}

{{PMID Auto
|PMID=23313272
|Title=An association study of suicide and candidate genes in the serotonergic system.
}}

{{PMID Auto
|PMID=23510579
|Title=Worldwide population variation and haplotype analysis at the serotonin transporter gene SLC6A4 and implications for association studies.
}}

{{PMID Auto
|PMID=23630162
|Title=Common and rare alleles of the serotonin transporter gene, SLC6A4, associated with Tourette's disorder.
}}

{{PMID Auto
|PMID=24776739
|Title=Multimodal imaging of a tescalcin (TESC)-regulating polymorphism (rs7294919)-specific effects on hippocampal gray matter structure
}}

{{PMID Auto
|PMID=25214390
|Title=Interaction among childhood trauma and functional polymorphisms in the serotonin pathway moderate the risk of depressive disorders
}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}