{"id":12817,"date":"2022-09-17T21:54:58","date_gmt":"2022-09-17T18:54:58","guid":{"rendered":"http:\/\/blog.ulubat.org\/?p=12817"},"modified":"2022-09-17T21:55:01","modified_gmt":"2022-09-17T18:55:01","slug":"intiharin-genetik-analizi","status":"publish","type":"post","link":"https:\/\/blog.ulubat.org\/index.php\/genel\/intiharin-genetik-analizi\/","title":{"rendered":"\u0130ntihar\u0131n Genetik Analizi"},"content":{"rendered":"
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\"\"<\/a><\/figure><\/div>\n\n\n

Giri\u015f<\/strong><\/h2>\n\n\n\n

D\u00fcnyada her y\u0131l 700.000’den fazla insan intihar ediyor. Ve bu aileleri ve toplumu \u00e7ok\u00e7a etkileyen bir trajedidir. \u0130ntihar, 2016 y\u0131l\u0131nda 15-29 ya\u015f\u0131ndaki ki\u015filer aras\u0131nda ikinci s\u0131radaki \u00f6l\u00fcm nedeniydi. En yayg\u0131n y\u00f6ntemler; kendini asmak, zehirlemek ve ate\u015fli silahlard\u0131. Bilimsel kan\u0131tlardan biliyoruz ki intihar davran\u0131\u015f\u0131na genetik bir yatk\u0131nl\u0131k vard\u0131r. <\/p>\n\n\n\n

Bug\u00fcn bu yaz\u0131da 2022 y\u0131l\u0131nda \u0130talya’da yap\u0131lan intihar\u0131n genetik analizi ile ilgili olan bir \u00e7al\u0131\u015fmay\u0131 \u00f6zetleyece\u011fim. \u00c7al\u0131\u015fmada 2007 ve 2017 y\u0131llar\u0131 aras\u0131nda intihar eden 111 ki\u015fiyi incelemektedir. DNA \u00f6rnekleri ile \u00e7oklu n\u00f6robiyolojik yolaklardan 22 gen ara\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r.<\/p>\n\n\n\n

<\/p>\n\n\n\n

Se\u00e7ilen Genler <\/strong><\/h2>\n\n\n\n

Dopamin resept\u00f6r\u00fc D4 (DRD4) geni, bir dizi damgalanm\u0131\u015f gen bar\u0131nd\u0131ran CpG adalar\u0131n\u0131 i\u00e7eren bir kromozomal b\u00f6lgede yer al\u0131r. Bu genin \u00fc\u00e7\u00fcnc\u00fc ekzonundaki de\u011fi\u015fken say\u0131da ard\u0131\u015f\u0131k tekrarlar birka\u00e7 grup taraf\u0131ndan ara\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r. 5-hidroksitriptamin resept\u00f6r\u00fcndeki (HTR1A, HTR1B, HTR2A ve HTR2C) ve ayr\u0131ca serotonin ta\u015f\u0131y\u0131c\u0131 (SLC6A4) genlerindeki bir\u00e7ok SNP, VNTR ve allel, agresifli\u011fi veya intihar e\u011filimlerini etkileyebildi\u011fi i\u00e7in bu polimorfozimler de \u00e7al\u0131\u015fmaya dahil edilmi\u015ftir. <\/p>\n\n\n\n

(SNP-Single nucleotide polymorphism- DNA sekans\u0131nda tek bir n\u00fckleotidin farkl\u0131 olmas\u0131d\u0131r.VNTR-variable number tandem repeats- DNA profillemesinde genomda tekrar eden diziler kullan\u0131l\u0131r. Bu diziler de\u011fi\u015fken say\u0131l\u0131 biti\u015fik tekrarlar olarak adland\u0131r\u0131l\u0131r.)<\/p>\n\n\n\n

Serotonin-ta\u015f\u0131y\u0131c\u0131ya ba\u011fl\u0131 polimorfik b\u00f6lgenin (5-HTTLPR) k\u0131sa vadeli yeniden intihar giri\u015fimi riskinin bir \u00f6ng\u00f6r\u00fcc\u00fcs\u00fc oldu\u011fu bildirilmektedir. Adrenosept\u00f6r Alfa 2 A (ADRA2A) genindeki varyasyonlar intihar ve i\u00e7ine kapan\u0131k davran\u0131\u015f vakalar\u0131nda tan\u0131mlan\u0131r. Nitrik oksit sentaz\u0131n (NOS I) n\u00f6ronal izoformunun sald\u0131rganl\u0131\u011f\u0131 i\u00e7eren \u00e7e\u015fitli davran\u0131\u015flar\u0131 de\u011fi\u015ftirdi\u011fi tespit edilmi\u015ftir. NOS I Exon 1f’deki promot\u00f6r VNTR’yi analiz etmek yerine istatistiksel olarak anlaml\u0131 herhangi bir fark\u0131 do\u011frulamak i\u00e7in pop\u00fclasyondaki ve kontrol grubundaki SNP varyasyonu incelenmi\u015ftir. Monoamin oksidaz A (MAOA) VNTR’leri aras\u0131ndaki ba\u011flant\u0131y\u0131 inceleyen \u00e7al\u0131\u015fmalar, belirli vakalarda psikiyatrik hastalarla istatistiksel olarak anlaml\u0131 bir ba\u011f g\u00f6stermektedir. Katekol-O-metiltransferaz (COMT) gen varyasyonu, \u00f6zellikle Val108\/158Met polimorfizmi, yak\u0131n zamanda intiharlarla ili\u015fkilendirilmi\u015ftir.<\/p>\n\n\n\n

Beyin kaynakl\u0131 n\u00f6rotrofik fakt\u00f6r (BDNF) genindeki spesifik aleller veya SNP’lerin \u015fizofreninin etiyolojisi \u00fczerinde n\u00f6robiyolojik etkileri vard\u0131r. Dopamin resept\u00f6r\u00fc (DRD2) genindeki se\u00e7ilen SNP’ler, alkol ba\u011f\u0131ml\u0131l\u0131\u011f\u0131 ve di\u011fer ili\u015fkili bozukluklar\u0131n geli\u015fimi i\u00e7in olas\u0131 genetik risk fakt\u00f6rleridir. Bu SNP’ler intihar giri\u015fiminde incelenmi\u015ftir. Sodyum kanal\u0131 voltaj kap\u0131l\u0131 tip VIII alfa polipeptidi (SCN8A), vezik\u00fclle ili\u015fkili membran proteini 4 (VAMP4) ve prenile Rab al\u0131c\u0131 1 (RABAC1) genlerindeki veya bunlara biti\u015fik gen varyantlar\u0131, intihar giri\u015fimlerinde a\u015f\u0131r\u0131 aktif hale gelir. Son olarak, cAMP-yan\u0131t eleman\u0131 ba\u011flay\u0131c\u0131 proteinlerde (CREB1) polimorfizmlerindeki varyasyonlarla \u00f6nemli ba\u011flar bulunmu\u015ftur. <\/p>\n\n\n\n

<\/p>\n\n\n\n

Genetik Sonu\u00e7lar\u0131<\/strong><\/h2>\n\n\n\n

\u00c7al\u0131\u015fmada istatistiksel olarak anlaml\u0131 19 varyant tan\u0131mlanm\u0131\u015ft\u0131r. Tan\u0131mlanan gen varyantlar\u0131ndan yedisi daha \u00f6nce hi\u00e7 g\u00f6zlemlenmemi\u015f, yedisi kontrol pop\u00fclasyonunda daha d\u00fc\u015f\u00fck bir s\u0131kl\u0131\u011fa sahip ve \u00fc\u00e7\u00fc genel pop\u00fclasyondan %0.5’ten daha az s\u0131kl\u0131\u011fa sahiptir. SLC6A4 ve CREB1’de olan mutasyonlar kodlanm\u0131\u015f amino asidi de\u011fi\u015ftirmeyen e\u015f anlaml\u0131 mutasyonlard\u0131r. MAOA, HTR2A, SCN8A ve NOS3 mutasyonlar\u0131 ise yanl\u0131\u015f anlaml\u0131 mutasyonlard\u0131r. <\/p>\n\n\n\n

MAOA>arjininden triptofana<\/p>\n\n\n\n

HTR2A>metiyoninden treonine<\/p>\n\n\n\n

SCN8A>alaninden serine<\/p>\n\n\n\n

NOS3>fenilalaninden l\u00f6sine amino asit de\u011fi\u015fikli\u011fini g\u00f6sterir.<\/p>\n\n\n\n

Bu e\u015f anlaml\u0131 olmayanlar, bu genlerin protein \u00fcr\u00fcn\u00fcn\u00fc ve biyofiziksel \u00f6zelliklerini de\u011fi\u015ftirerek, proteinin i\u015flevinin de de\u011fi\u015febilece\u011fini d\u00fc\u015f\u00fcnd\u00fcrtm\u00fc\u015ft\u00fcr. SNV, DRD2 transkripsiyonel ba\u015flang\u0131\u00e7 \u200b\u200bb\u00f6lgesinin yukar\u0131 ak\u0131\u015f\u0131nda yedi baz \u00e7ifti g\u00f6zlemlemesine ra\u011fmen, protein dizisini etkilemeyecek olsa da, transkripsiyon fakt\u00f6rlerinin veya mikroRNA’lar\u0131n ba\u011flanma afinitesini etkileyerek konak\u00e7\u0131 veya distal genlerin transkripsiyonel aktivitesi \u00fczerinde muhtemelen bir etkisi olabilece\u011fi g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. <\/p>\n\n\n\n

Genel pop\u00fclasyonla kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda seride g\u00f6zlemlenen daha d\u00fc\u015f\u00fck s\u0131kl\u0131\u011fa sahip yedi varyanttan ikisi DRD4 geninin kodlama b\u00f6lgesindeydi ve biri e\u015f anlaml\u0131 di\u011feri shift idi. E\u015f anlaml\u0131 varyant daha \u00f6nce intihar davran\u0131\u015f\u0131 ile ili\u015fkili oldu\u011fu g\u00f6sterilen bir VNTR’dir. ACE geninde potansiyel koruyucu rol\u00fc olan d\u00f6rt varyant mevcuttur. Son olarak, NOS3’teki varyant geni, ekson 7’de aspartik asidin glutamik aside amino asit de\u011fi\u015fimine yol a\u00e7an bir yanl\u0131\u015f anlaml\u0131 mutasyondur. Bu iyi huylu olarak rapor edilmektedir. <\/p>\n\n\n\n

Elde edilen sonu\u00e7lardan bu kohort \u00e7al\u0131\u015fmas\u0131nda intiharla birka\u00e7 potansiyel genetik ba\u011flant\u0131n\u0131n alt\u0131 \u00e7izilmi\u015ftir. Bu da pop\u00fclasyondaki belirli genetik varyantlar ile intihar davran\u0131\u015f\u0131 aras\u0131ndaki ili\u015fkiyi destekler.<\/p>\n\n\n\n

<\/p>\n\n\n

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\"\"<\/a><\/figure><\/div>\n\n\n

Kaynak\u00e7a<\/strong><\/h2>\n\n\n\n
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  • Zai CC, Tiwari AK, Basile V, et al. Association study of tardive dyskinesia and five DRD4 polymorphisms in schizophrenia patients. Pharmacogenomics J. 2009;9:168\u2013174. [Crossref], [Web of Science \u00ae], [Google Scholar]<\/li>
  • https:\/\/doi.org\/10.1080\/20961790.2020.1835156<\/li><\/ul>\n","protected":false},"excerpt":{"rendered":"

    Giri\u015f D\u00fcnyada her y\u0131l 700.000’den fazla insan intihar ediyor. Ve bu aileleri ve toplumu \u00e7ok\u00e7a etkileyen bir trajedidir. \u0130ntihar, 2016<\/p>\n","protected":false},"author":1138,"featured_media":12819,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1,2173,25],"tags":[2371,73,149,115,125,66],"acf":[],"views":343,"_links":{"self":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/12817"}],"collection":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/users\/1138"}],"replies":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/comments?post=12817"}],"version-history":[{"count":3,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/12817\/revisions"}],"predecessor-version":[{"id":12825,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/12817\/revisions\/12825"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media\/12819"}],"wp:attachment":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media?parent=12817"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/categories?post=12817"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/tags?post=12817"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}