{"id":6227,"date":"2020-07-15T01:16:59","date_gmt":"2020-07-14T22:16:59","guid":{"rendered":"http:\/\/blog.ulubat.org\/?p=6227"},"modified":"2020-12-31T04:56:57","modified_gmt":"2020-12-31T01:56:57","slug":"singapurda-saglik-ve-genetik","status":"publish","type":"post","link":"https:\/\/blog.ulubat.org\/index.php\/genel\/singapurda-saglik-ve-genetik\/","title":{"rendered":"Singapur’da Sa\u011fl\u0131k ve Genetik"},"content":{"rendered":"\n
\"\"
(Test t\u00fcpleri. G\u00f6rsel Kayna\u011f\u0131: angellodeco\/Shutterstock<\/a>)<\/figcaption><\/figure>\n\n\n\n

Malezyal\u0131 Erkek \u00c7ocuklarda Akut Lenfoblastik L\u00f6semi (ALL)<\/p>\n\n\n\n

Uterusta a\u00e7\u0131\u011fa \u00e7\u0131kt\u0131\u011f\u0131 d\u00fc\u015f\u00fcn\u00fclen ALL, \u00e7ocuk kanserlerinin b\u00fcy\u00fck b\u00f6l\u00fcm\u00fcn\u00fc olu\u015fturur. Sebebinin ise genetik duyarl\u0131l\u0131k ile fetal ve bebeklik d\u00f6nemlerinde maruz kal\u0131nan kanserojen maddeler oldu\u011fu \u00f6ne s\u00fcr\u00fcl\u00fcyor. Folat metabolizmas\u0131n\u0131n da cinsiyete g\u00f6re farkl\u0131l\u0131k g\u00f6sterdi\u011fi bulunmu\u015ftur ve l\u00f6semiyle ili\u015fkilidir.  <\/p>\n\n\n\n

Malezyal\u0131 erkek \u00e7ocuklarda l\u00f6semiye kar\u015f\u0131 koruyucu \u00f6zelli\u011fe sahip bir genotip tespit edilmi\u015ftir. Fakat bu \u00f6zellik etnik k\u00f6kene g\u00f6re de\u011fi\u015fmektedir. Ayn\u0131 \u00e7al\u0131\u015fmada \u00c7inli erkek \u00e7ocuklar\u0131n l\u00f6semiye e\u011filiminin k\u0131zlara g\u00f6re daha \u00e7ok oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. <\/p>\n\n\n\n

QnrB <\/em>Geninin Tespiti ve \u0130ncelenmesi<\/p>\n\n\n\n

Enterobacteriaceae <\/em>ailesine mensup gram negatif E. coli, Klebsiella, Salmonella <\/em>ve Shigella <\/em>gibi bakteriler Qnr <\/em>genlerine sahiptir. Bu genler plazmidde bulunur ve Kinolon direnci sa\u011flar. QnrA, QnrB <\/em>ve QnrS <\/em>olarak \u00fc\u00e7 gruba ayr\u0131l\u0131r. Bu genlerin DNA giraz ve topoizomeraz IV\u2019e ba\u011fland\u0131\u011f\u0131 ve bu \u015fekilde enzimleri Kinolon inhibisyonundan korudu\u011fu d\u00fc\u015f\u00fcn\u00fcl\u00fcyor. Ama QnrB <\/em>geni di\u011fer ikisine g\u00f6re daha zay\u0131f bir koruma sa\u011fl\u0131yor. G\u00f6reviyse DNA mutasyonlar\u0131n\u0131n \u00f6nlenmesidir. <\/p>\n\n\n\n

Qnr <\/em>genlerinin bakteriler aras\u0131nda ta\u015f\u0131nma kolayl\u0131\u011f\u0131, b\u00fcy\u00fck plasmidler \u00fczerinde mobilitesi y\u00fcksek par\u00e7alar\u0131n i\u00e7inde veya yan\u0131nda olmalar\u0131 sayesindedir. Singapur\u2019da bir \u00e7al\u0131\u015fmada QnrB<\/em> genine sahip Klebsiella Pneumoniae <\/em>bakterisinin bir\u00e7ok antibiyoti\u011fe diren\u00e7li oldu\u011fu bulunmu\u015ftur. Bu antibiyotikler aras\u0131nda Aminoglikozidler, Beta-laktamlar, Dihidrofolat red\u00fcktaz, Sulfametoksazol ve Tetrasiklin bulunur. \u00c7al\u0131\u015fmaya g\u00f6re bu gen QnrA <\/em>ve QnrS <\/em>genlerinin bulundu\u011fu plasmid b\u00f6lgelerinden farkl\u0131 noktalarda bulunmaktad\u0131r. Bu b\u00f6lgelerin bir k\u0131sm\u0131 bu ara\u015ft\u0131rmada ke\u015ffedilmi\u015ftir. <\/p>\n\n\n\n

\"\"
(Laboratuvar. G\u00f6rsel Kayna\u011f\u0131: Gorodenkoff\/Shutterstock<\/a>, ID: 1073659406)<\/figcaption><\/figure>\n\n\n\n

PARP \u0130nhibit\u00f6r\u00fc ve Yumurtal\u0131k Kanseri<\/p>\n\n\n\n

PARP inhibit\u00f6r\u00fc kanseri \u00f6nleyici \u00f6zelli\u011fe sahip bir proteindir ve kanser tedavilerinde kullan\u0131lmaktad\u0131r. Ancak bu proteinin kanseri olumsuz etkileyen bir y\u00f6n\u00fc Singapur\u2019da g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. PARP inhibit\u00f6r\u00fcn\u00fcn kullan\u0131ld\u0131\u011f\u0131 yumurtal\u0131k kanseri tedavilerinde, kullan\u0131lmad\u0131\u011f\u0131 tedavilere g\u00f6re hastal\u0131k daha \u00e7ok n\u00fcksetmi\u015ftir. Hastal\u0131\u011f\u0131n n\u00fcksetti\u011fi ki\u015filerin mutasyona u\u011fram\u0131\u015f BRCA1 ya da BRCA2 geni ta\u015f\u0131d\u0131\u011f\u0131 d\u00fc\u015f\u00fcn\u00fcl\u00fcyor. Ayr\u0131ca PARP inhibit\u00f6r\u00fc Sisplatin ve Temozolomid\u2019in hasar verdi\u011fi DNA\u2019y\u0131 onar\u0131r ve mitokondrinin bozulmas\u0131n\u0131 engeller.<\/p>\n\n\n\n

Alerji ve Atopik Dermatit<\/p>\n\n\n\n

BDNF (Brain Derived\nNeurotrophic Factor \u2013 Beyin T\u00fcrevli N\u00f6rotrofik Fakt\u00f6r) normalde geli\u015fim \u00e7a\u011f\u0131nda\nsa\u011fl\u0131kl\u0131 bireylerde sinir sisteminin olu\u015fumu, olgunla\u015fmas\u0131 ve korunmas\u0131nda\ng\u00f6rev al\u0131r. Eri\u015fkinlerde ise sinaptik esneklik, dendrit geli\u015fimi ve uzun\nd\u00f6nemli haf\u0131za i\u00e7in \u00f6nemlidir. Ayr\u0131ca BDNF gibi \u00e7e\u015fitli n\u00f6rotrofinleri\nmakrofajlar, eozinofinler, mast h\u00fccreleri ve B ve T h\u00fccreleri de \u00fcretir. Hem\nperiferal hem de merkezi sinir sisteminde salg\u0131lanabilirler.<\/p>\n\n\n\n

Alerjik hastal\u0131klar ve\natopik dermatit (egzama) d\u00fcnya \u00fczerindeki d\u00f6rt ki\u015fiden en az birini etkiler. Bu\nhastal\u0131klar hem genetik hem de \u00e7evresel fakt\u00f6rlere ba\u011fl\u0131 geli\u015fir. Singapur\u2019da\nya\u015fayan \u00c7inlilerde de BDNF\u2019nin  alerjik\nast\u0131m ve alerjik rinit ile ili\u015fkili oldu\u011fu bulunmu\u015ftur. BDNF\u2019nin kan,\nbronkoalveolar ve burun s\u0131v\u0131s\u0131ndaki miktar\u0131 artt\u0131k\u00e7a bu iki alerjik hastal\u0131\u011f\u0131n\nve egzaman\u0131n \u015fiddeti de artmaktad\u0131r. \u0130ltihapl\u0131 h\u00fccrelerde, \u00f6rne\u011fin hava\nyollar\u0131nda, yan\u0131t olarak sitokinler ve IgE antikorlar\u0131 salg\u0131lan\u0131r. Bunlar\niltihapl\u0131 h\u00fccreleri iyile\u015ftirmede g\u00f6rev al\u0131r. Fakat bu alerjik inflamasyon BDNF\u2019yi\ninhibe ederek sinir sisteminin i\u015flevini yitirmesine yol a\u00e7ar. BDNF gibi n\u00f6rotrofinler\nn\u00f6ronlarda inhibe olmas\u0131na ra\u011fmen alerjik hastal\u0131klarda serum seviyesi artar. Salg\u0131land\u0131\u011f\u0131\nb\u00f6lgede yap\u0131sal de\u011fi\u015fimlere neden olur. <\/p>\n\n\n\n

BDNF geni 11p13 kromozomunda bulunur. Farkl\u0131 toplumlarda bu genin polimorfizmine ba\u011fl\u0131 olarak farkl\u0131 alerji fenotipleri bulunabilir. Polimorfizmin h\u00fccre trafi\u011fini ve BDNF\u2019nin salg\u0131lan\u0131\u015f\u0131n\u0131 etkiledi\u011fi g\u00f6sterilmi\u015ftir. Singapur\u2019da \u00c7inliler \u00fcst\u00fcnde yap\u0131lan \u00e7al\u0131\u015fmada da BDNF\u2019nin n\u00f6rodejeneratif hastal\u0131klar \u00fcst\u00fcnde terap\u00f6tik etkinli\u011finin olabilece\u011fi bulunmu\u015ftur. <\/p>\n\n\n\n

Stres ve enfeksiyon durumunda salg\u0131lanan sitokinler ve uyard\u0131klar\u0131 astrositler BDNF\u2019nin n\u00f6ron ile etkile\u015fimini inhibe etmektedir. Bu da n\u00f6ronun hayatta kalmas\u0131n\u0131 \u00f6nler.<\/p>\n\n\n\n

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

Singapur\u2019da ya\u015fayan \u00c7inlilerde\nCTNND2 geninin varyasyonundan kaynakl\u0131 derecesi y\u00fcksek miyopluk g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Bu\nDo\u011fu Asya \u00fclkeleri i\u00e7in normal bir durumdur ve 40-79 ya\u015f aral\u0131\u011f\u0131ndaki\n\u00c7inlilerin %40\u2019\u0131nda miyopluk bulunur. Singapur\u2019daki \u00c7inliler \u00fczerinde miyopla\nilgili yap\u0131lan ilk genom ili\u015fkilendirme \u00e7al\u0131\u015fmas\u0131nda (GWAS) 11q24.1\nkromozomunun bu hastal\u0131\u011fa duyarl\u0131 bir lokusu oldu\u011fu saptanm\u0131\u015ft\u0131r. <\/p>\n\n\n\n

Folilpoliglutamat Sentaz\n(FPGS), Gama Glutamil Hidrolaz (GGH) ve Plazma Homosistein Seviyesi (PHS)<\/p>\n\n\n\n

Yine Singapur\u2019da \u00c7inliler\n\u00fczerinde yap\u0131lan bir \u00e7al\u0131\u015fmada FPGS, GGH ve PHS genetik varyasyonlar\u0131\nincelenmi\u015ftir. Tek karbonlu metabolizmada folat\u0131n bir vitamin olarak \u00f6nemli bir\nyeri oldu\u011fu i\u00e7in eksikli\u011fi bir\u00e7ok kronik hastal\u0131\u011fa yol a\u00e7abilir. Baz\u0131 enzimler\nbu hastal\u0131klarla ili\u015fkilidir. \u0130ncelenen FPGS ve GGH enzimleri de glutamat\u0131\nfolata ekleyerek (FPGS) ya da \u00e7\u0131kararak (GGH) folat\u0131n h\u00fccre homeostaz\u0131n\u0131\nsa\u011flar. Glutamat eklenirse folat h\u00fccre i\u00e7erisinde daha uzun kal\u0131r. Yap\u0131lan\nincelemede FPGS\u2019nin PHS\u2019yi etkilemedi\u011fi ancak GGH\u2019nin etkiledi\u011fi bulunmu\u015ftur.\nGGH\u2019nin bir aleli olan G\u2019nin ise DNA urasil i\u00e7eri\u011fiyle ili\u015fkili oldu\u011fu\ng\u00f6r\u00fclm\u00fc\u015ft\u00fcr. <\/p>\n\n\n\n

\"\"
(Do\u011fal ila\u00e7 ara\u015ft\u0131rmas\u0131 yapan bilim adam\u0131. G\u00f6rsel Kayna\u011f\u0131: ARTFULLY PHOTOGRAPHER\/Shutterstock<\/a>, ID: 1481963861)<\/figcaption><\/figure>\n\n\n\n

Monokarboksilat Transport (MCT) Proteinleri<\/p>\n\n\n\n

MCT ailesine mensup\nproteinler laktat, piruvat, asetat ve ketonlar\u0131 ta\u015f\u0131r. 14 \u00fcyesi vard\u0131r ve ilk\nd\u00f6rd\u00fc (MCT1-MCT4) \u00e7ok \u00f6nemli ta\u015f\u0131ma g\u00f6revlerine sahiptir. MCT1 v\u00fccudun her\nyerinde bulunmakla birlikte en \u00e7ok kalp ve k\u0131rm\u0131z\u0131 kas h\u00fccrelerinde yer al\u0131r,\negzersizde i\u015flevi artar ve laktik asit oksidasyonunda \u00f6nemli bir rol al\u0131r. MCT4\nise glikolitik aktivitesi y\u00fcksek dokularda daha \u00e7oktur. Bunlar aras\u0131nda beyaz \u00e7izgili\nkas h\u00fccreleri, astrositler, beyaz kan h\u00fccreleri, plasenta ve kondrositler bulunur.\nLaktik asit ak\u0131\u015f\u0131nda \u00f6nemli rol oynar. MCT1 ve MCT4, \u00e7izgili kaslar i\u00e7in MCT\nailesinin en \u00f6nemli izoformlar\u0131d\u0131r. Bu da laktik asidin farkl\u0131 tip kas\nh\u00fccrelerine ak\u0131\u015f\u0131n\u0131 sa\u011flar. B\u00f6ylece pH\u2019n\u0131n d\u00fc\u015fmesiyle enzim aktivitesi azal\u0131r\nve kaslar\u0131n \u00e7al\u0131\u015f\u0131p daha fazla laktik asit \u00fcretmesi engellenir. Ayr\u0131ca MCT\nailesi ila\u00e7lar\u0131 da ta\u015f\u0131r. <\/p>\n\n\n\n

Singapur \u00c7in ve Hintlileri\n\u00fcst\u00fcnde yap\u0131lan \u00e7al\u0131\u015fmalarda MCT4\u2019\u00fc kodlayan genin SNP\u2019si (Single Nucleotide\nPolymorphism \u2013 Tek N\u00fckleotid Polimorfizmi) incelenmi\u015ftir. SIFT algoritmas\u0131\n(Scale-Invariant Feature Transform \u2013 \u00d6l\u00e7ek-De\u011fi\u015fmez \u00d6zellik D\u00f6n\u00fc\u015f\u00fcm\u00fc) genler\naras\u0131ndaki homolojiyi inceleyerek olu\u015fan proteindeki 20 farkl\u0131 amino asidin\netkisini tahmin edebilmektedir. PhyloPhen ise yap\u0131sal \u00f6zelliklere bakarak\nfarkl\u0131 varyasyonlar\u0131 inceler. Bulgulara g\u00f6re MCT4\u2019\u00fcn 465 amino asidi ve 12\ntransmembran b\u00f6lgesi bulunmaktad\u0131r. Azot ve karbon u\u00e7lar\u0131 da sitoplazmadad\u0131r. MCT1\u2019in\nde 7 farkl\u0131 varyant\u0131 tespit edilmi\u015ftir ve bunlar\u0131n d\u00f6rd\u00fc bu \u00e7al\u0131\u015fmalarda ke\u015ffedilmi\u015ftir.\nVaryantlar, MCT1\u2019in kodlanma \u015feklini etkiliyor olabilir. Singapur\u2019da yap\u0131lan bu\n\u00e7al\u0131\u015fmalar MCT\u2019ler hakk\u0131nda ileriki \u00e7al\u0131\u015fmalar i\u00e7in temel olu\u015fturmaktad\u0131r. <\/p>\n\n\n\n

Bilgi Kaynak\u00e7as\u0131<\/p>\n\n\n\n

  1. ScienceDirect. Andiappan, Anand Kumar. Parate, Pallavi Nilkanth. Anantharaman, Ramani. Suri, Bani Kaur. Wang, De Yun. Chew, Fook Tim. \u201cGenetic variation in BDNF is associated with allergic asthma and allergic rhinitis in an ethnic Chinese population in Singapore\u201d Cytokine. <\/em>(56):2, 218-223. Kas\u0131m 2011. <\/li>
  2. ScienceDirect. Li, Yi-Ju. Goh, Liang. Khor, Chiea-Chuen. Fan, Qiao. Yu, Miao. Han, Siyu. Sim, Xueling. Ong, Rick Twee-Hee. Wong, Tien-Yin. Vithana, Eranga Nishanthie. Yap, Eric. Nakanishi, Hideo. Matsuda, Fumihiko. Ohno-Matsui, Kyoko. Yoshimura, Nagahisa. Seielstad, Mark. Tai, E.-Shyong. L. Young, Terri. Saw, Seang-Mei. \u201cGenome-Wide Association Studies Reveal Genetic Variants in CTNND2 for High Myopia in Singapore Chinese\u201d Ophthalmology. <\/em>(118):2, 368-375. \u015eubat 2011. <\/li>
  3. ScienceDirect. J. Oppeneer, Sarah. A. Ross, Julie. Koh, Woon-Puay. Yuan, Jian-Min. Robien, Kim. \u201cGenetic variation in folylpolyglutamate synthase and gamma-glutamyl hydrolase and plasma homocysteine levels in the Singapore Chinese Health Study\u201d Molecular Genetics and Metabolism. <\/em>(105):1, 73-78. Ocak 2012. <\/li>
  4. ScienceDirect. Bee Lean, Choo. Jon Deoon Lee, Edmund. \u201cGenetic Variations of the MCT4 (SLC16A3) Gene in the Chinese and Indian Populations of Singapore\u201d Drug Metabolism and Pharmacokinetics. <\/em>(27):4, 456-464. 2012. <\/li>
  5. ScienceDirect. Bee Lean, Choo. Jon Deoon Lee, Edmund. \u201cGenetic Variations in the MCT1 (SLC16A1) Gene in the Chinese Population of Singapore\u201d Drug Metabolism and Pharmacokinetics. <\/em>(24):5, 469-474. 2009. <\/li>
  6. ScienceDirect. Eng-Juh Yeoh, Allen. Lu, Yi. Yong-Sheng Chan, Jason. Huak Chan, Yiong. Ariffin, Hany. Kow-Yin Kham, Shirley. Chong Quah, Thuan. \u201cGenetic susceptibility to childhood acute lymphoblastic leukemia shows protection in Malay boys: Results from the Malaysia-Singapore ALL Study Group\u201d Leukemia Research. <\/em>(34):3, 276-283. Mart 2010. <\/li>
  7. ScienceDirect. Woon Pei Teo, Jeanette. Kg, Kah Ying. Tzer Pin Lin, Raymond. \u201cDetection and genetic characterisation of qnrB in hospital isolates of Klebsiella pneumoniae in Singapore\u201d International Journal of Antimicrobial Agents. <\/em>(33):2, 177-180. \u015eubat 2009. <\/li>
  8. ScienceDirect. Halkman, H.B.D.. Halkman, A.K.. \u201cIndicator Organisms\u201d Encyclopedia of Food Microbiology (Second Edition). <\/em>358-363. 2014. <\/li>
  9. ScienceDirect. Ong, P.Y.. Tan, D.S.. Aung, K.S.. Er, J.B.T.. Lee, S.C.. \u201cImpact of PARP inhibitor expanded access program on the uptake of genetic testing in newly diagnosed or recurrent ovarian cancer patients in Singapore\u201d Gynecologic Oncology. <\/em>(145):1, 76-77. Haziran 2017. <\/li><\/ol>\n\n\n\n

    G\u00f6rsel Kaynak\u00e7as\u0131<\/p>\n\n\n\n

    1. angellodeco\/Shutterstock<\/a><\/li>
    2. Gorodenkoff\/Shutterstock<\/a>, ID: 1073659406<\/li>
    3. ARTFULLY PHOTOGRAPHER\/Shutterstock<\/a>, ID: 1481963861<\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"

      Malezyal\u0131 Erkek \u00c7ocuklarda Akut Lenfoblastik L\u00f6semi (ALL) Uterusta a\u00e7\u0131\u011fa \u00e7\u0131kt\u0131\u011f\u0131 d\u00fc\u015f\u00fcn\u00fclen ALL, \u00e7ocuk kanserlerinin b\u00fcy\u00fck b\u00f6l\u00fcm\u00fcn\u00fc olu\u015fturur. Sebebinin ise genetik<\/p>\n","protected":false},"author":267,"featured_media":6231,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1,25],"tags":[708,736,811,814,493,187,825,823,813,817,115,810,826,55,822,812,824,815,120,821,265,820,818,816,169],"acf":[],"views":668,"_links":{"self":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/6227"}],"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\/267"}],"replies":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/comments?post=6227"}],"version-history":[{"count":7,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/6227\/revisions"}],"predecessor-version":[{"id":9325,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/6227\/revisions\/9325"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media\/6231"}],"wp:attachment":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media?parent=6227"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/categories?post=6227"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/tags?post=6227"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}