Editing Serotonin transporter (section)

=== Length variation in 5-HTTLPR ===
{{main|5-HTTLPR}}

According to a 1996 article in ''The Journal of Neurochemistry'', the [[promoter (biology)|promoter]] region of the SLC6A4 gene contains a [[Polymorphism (biology)|polymorphism]] with "short" and "long" repeats in a region: 5-HTT-linked polymorphic region ([[5-HTTLPR]] or ''SERTPR'').<ref>{{cite journal | vauthors = Heils A, Teufel A, Petri S, Stöber G, Riederer P, Bengel D, Lesch KP | title = Allelic variation of human serotonin transporter gene expression | journal = Journal of Neurochemistry | volume = 66 | issue = 6 | pages = 2621–2624 | date = June 1996 | pmid = 8632190 | doi = 10.1046/j.1471-4159.1996.66062621.x | s2cid = 42037860 }}</ref>
The short variation has 14 repeats of a sequence while the long variation has 16 repeats.<ref name="NakamuraM2000Human"/> A second 1996 article stated that the short variation leads to less [[transcription (genetics)|transcription]] for SLC6A4, and it has been found that it can partly account for anxiety-related [[personality trait]]s.<ref>{{cite journal | vauthors = Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Müller CR, Hamer DH, Murphy DL | title = Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region | journal = Science | volume = 274 | issue = 5292 | pages = 1527–1531 | date = November 1996 | pmid = 8929413 | doi = 10.1126/science.274.5292.1527 | s2cid = 35503987 | bibcode = 1996Sci...274.1527L }}</ref> This polymorphism has been extensively investigated in over 300 scientific studies (as of 2006).<ref>{{cite journal | vauthors = Wendland JR, Martin BJ, Kruse MR, Lesch KP, Murphy DL | title = Simultaneous genotyping of four functional loci of human SLC6A4, with a reappraisal of 5-HTTLPR and rs25531 | journal = Molecular Psychiatry | volume = 11 | issue = 3 | pages = 224–226 | date = March 2006 | pmid = 16402131 | doi = 10.1038/sj.mp.4001789 | s2cid = 26655014 | doi-access =  }}</ref> The 5-HTTLPR polymorphism may be subdivided further:
One study published in 2000 found 14 [[allele|allelic]] variants (14-A, 14-B, 14-C, 14-D, 15, 16-A, 16-B, 16-C, 16-D, 16-E, 16-F, 19, 20 and 22) in a group of around 200 [[Japanese people|Japanese]] and [[Caucasian race|Caucasian]] people.<ref name="NakamuraM2000Human"/>

In addition to altering the expression of SERT protein and concentrations of extracellular serotonin in the brain, the 5-HTTLPR variation is associated with changes in brain structure.  One 2005 study found less [[grey matter]] in perigenual [[anterior cingulate cortex]] and [[amygdala]] for short allele carriers of the [[5-HTTLPR]] polymorphism compared to subjects with the long/long genotype.<ref name="Pezawas2005">{{cite journal | vauthors = Pezawas L, Meyer-Lindenberg A, Drabant EM, Verchinski BA, Munoz KE, Kolachana BS, Egan MF, Mattay VS, Hariri AR, Weinberger DR | title = 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression | journal = Nature Neuroscience | volume = 8 | issue = 6 | pages = 828–834 | date = June 2005 | pmid = 15880108 | doi = 10.1038/nn1463 | s2cid = 1864631 }}</ref>

In contrast, a 2008 meta-analysis found no significant overall association between the 5-HTTLPR polymorphism and autism.<ref name=Huang-Santangelo>{{cite journal | vauthors = Huang CH, Santangelo SL | title = Autism and serotonin transporter gene polymorphisms: a systematic review and meta-analysis | journal = American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics | volume = 147B | issue = 6 | pages = 903–913 | date = September 2008 | pmid = 18286633 | doi = 10.1002/ajmg.b.30720 | s2cid = 9491697 }}</ref> A hypothesized [[gene–environment interaction]] between the short/short allele of the 5-HTTLPR and life stress as predictor for [[major depressive disorder|major depression]] has suffered a similar fate: after an influential<ref>{{cite journal | vauthors = Nierenberg AA | title = The long tale of the short arm of the promoter region for the gene that encodes the serotonin uptake protein | journal = CNS Spectrums | volume = 14 | issue = 9 | pages = 462–463 | date = September 2009 | pmid = 19890228 | doi = 10.1017/s1092852900023506 | s2cid = 24236284 }}</ref> initial report in 2003<ref>{{cite journal | vauthors = Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R | title = Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene | journal = Science | volume = 301 | issue = 5631 | pages = 386–389 | date = July 2003 | pmid = 12869766 | doi = 10.1126/science.1083968 | s2cid = 146500484 | bibcode = 2003Sci...301..386C }}</ref> there were mixed results in replication in 2008,<ref>{{cite journal | vauthors = Uher R, McGuffin P | title = The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis | journal = Molecular Psychiatry | volume = 13 | issue = 2 | pages = 131–146 | date = February 2008 | pmid = 17700575 | doi = 10.1038/sj.mp.4002067 | s2cid = 24432263 | doi-access =  }}</ref> and a 2009 meta-analysis was negative.<ref>{{cite journal | vauthors = Risch N, Herrell R, Lehner T, Liang KY, Eaves L, Hoh J, Griem A, Kovacs M, Ott J, Merikangas KR | title = Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis | journal = JAMA | volume = 301 | issue = 23 | pages = 2462–2471 | date = June 2009 | pmid = 19531786 | pmc = 2938776 | doi = 10.1001/jama.2009.878 }}</ref> See [[5-HTTLPR]] for more information.