MANİSA’DA ŞİZOFREN HASTALARIN SİTOGENETİK ANALİZİ VE POLİMERAZ ZİNCİR REAKSİYONU İLE COMT( 21q11.2 ) GENİNİN TEŞHİSİ

Abstract

Şizofreni birçok davranış ve düşünce bozukluğuna neden olan çok sistemli psikiyatrik bozukluklardan biridir. Erken yaşlarda başlayarak hayat boyu süren, sonlanımı kötü olan bir hastalıktır. Biyokimyasal, anatomik ve genetik alanlardaki birçok ilerlemelere karşın şizofreni kendine özgü yaşantıları ve davranışsal belirtileri olan ve ancak bu belirtilerin gözlenmesi ile tanı konabilen bir hastalık olarak kalmaya devam etmektedir. Çalışmamızın amacı, DSM-IV (Ruhsal Bozuklukların Tanısal ve Sayımsal El Kitabı) kriterlerine göre şizofreni tanısı konmuş 50 hastanın (25 kadın ve 25 erkek) sitogenetik analizlerini yaparak, sayısal ve yapısal kromozom anomalilerini belirlemek ve Polimeraz Zincir Reaksiyonu (PZR) yöntemi ile 22q11.2 bölgesindeki cathecol-O-methyltransferase belirlemektir. Araştırmamızın sitogenetik analizinde lenfosit kültürü ve Giemsa-Tripsin (GTG) bantlaması yapılarak ışık mikroskobunda incelendi. Genomik DNA, periferik kandan Nucleospin izolasyon kiti ile elde edildi. Oligonukleotid primerler kullanılarak PZR yöntemi ile kromozom 22q11.2 bölgesindeki 109 baz çifti uzunluğundaki COMT geni elde edildi. PZR ürünü, %2 lik agaroz jelde yürütülüp jel görüntüleme sisteminde resimlendi. Bu ön çalışmada Manisa’da yaşayan şizofren hastalarda şizofrene yatkınlıkta aday genlerden cathecolO-methyltransferase (COMT) olarak kodlanan COMT (22.q11.2) geni saptanmış oldu

Keywords

• Şizofreni, 22q11.2 mikrodelesyonu, PZR, COMT

Identification of COMT Gene ( 22q11.2 ) by Polymerase Chain Reaction and Cytogenetic Analysis in Patients with Schizophrenia in Manisa

Abstract

Schizophrenia is one of the multisystemic diseases that cause many behavioral and thinking problems. It is an evil disease that begins in the childhood and goes till the end of life. Although there are lots of advances in biochemical, anatomical and genetical areas, schizophrenia remains to be a disease with its unique characteristics having its own life and behavioral symptoms. It is by means of observing these symptoms that the aim of our study is to determine the numerical or structural abnormalities with the disease is diagnosed cytogenetic analysis of 50 patients (25 female, 25 male) who were diagnosed as schizophrenia by using the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders), criteria and to identify the CathecolO-Methyltransferase (COMT) gene on 22q11.2 region by using Polymerase Chain Reaction (PCR) method. In cytogenetic analyse of our study lymphocyte culture and Giemsa-Tripsin (GTG) banding have been done and examined under light microscope. Genomic DNA was extracted from peripheral blood by using Nucleospin isolation kits. COMT gene which is 109 bp lenght and belongs to 22q11.2 chromosome is duplicated by PCR method using oligonucleotid primers. PCR product has been performed in %2 agarose gel and imaged by gel screening system. With this preliminary study the COM (22.q11.2) gene encoding cathecol-O-methyltransferase (COMT) a functional candidate gene for schizophrenia, was found in the patients with schizophrenia who were living in Manisa province

Keywords

• Schizophrenia, 22q11.2 microdeletion, PCR, COMT

References

1. Buckley P G, Mantipragada KK, Tapia-Paez I. A full coverage, high resolution human chromosome 22 genomic microarray for clinical and research applications. Human Molecular Genetics 2002, 11:3221-3229.
2. Williams JH, Owen JM, O’Donovan CM. Is COMT schizophrenia? . Schizophrenia Bulletin . 2007, 33(3): 635-641. gene for
3. Matsui A, İkeda T, et al. Progression of human breast cancers to the metastatic state is linked to genotypes of Catecol-O- methyltransferase. Cancer Lett 2000, 15: 23- 31.
4. Paguette B, Fortier PK, et al. Estrogen metabolism in lymphangioleiomyomatozis: catechol-o-methyltransferase pathway is not involved. Thorax 2000, 55: 574-578.
5. Dunning AM, Healey CS, et al. A systemic review of genetic polymorphisms and breast cancer risk. Review. Cancer Epidemiol Biomarkers. 1999, 8: 843-854.
6. Lachman HM, Morrow B, et al. Association 108/158 ofcodon methyltransferase gene polymorphism with the psychiatric menifestation of velo- cardiofacial syndrome. Am J Med Genet 1996, 67: 468-472. catechol-o
7. Daniels JK, Williams NM, Williams J, Jones LA, Cordna AG, Murphy KC, Spurlock G, Riley G, Scamber P, Asherson P, McGuffin P, Owen MJ. No evidence for allelic association between schizophrenia and a polymorphism determining high or low catechol-O methyltransferase activity. Am J Psychiatry 1996, 153: 268-270.
8. HendersonAS, Korten AE, Jorm AF, Jacomp PA, Christensen H, Radgers B, Tan X, Easteal S. COMT and DRD3 polymorphism, enviromental exposures, and personality traits related to common mental disorders. Am J Med Genet 2000, 7: 102-107.

9. Tursen U, Kaya I, Erdal ME, Derici E, Gunduz O, Ikizoglu G. Association between catechol-O-methyltransferase polymorphism and vitiligo. Arch Dermatol Res 2002, 294: 143-146.
10. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders,4th Edition, American Psychiatric Pres, Washington, DC, 1994.
11. Rotondo A, Mazzanti C, Dell’Osso L, Rucci P, Sullivan P, Bouanani S, Gonnelli C, Goldman D, Cassano B.C. Catechol O- Methyltransferase, Serotonin Transporter, and Tryptophan Hydroxylase Gene Polymorphisms in Bipolar Disorder Patients With and Without Comorbid Panic Disorder Am J Psychiatry January 2002, 159:23-29.
12. Haran B, Chebalco S, Flaishon L, Harpaz N, Valinsky L, Shachar I. Grb7 expression and cellular migration in chronic lymphocytic leukemia: a comparative studyof early and advanced stage disease. Leukemia 2004, 18: 1948-1950.
13. Jagannathan K, Calhoun VD, Gelernter J.Genetic associations of brain structural networks in schizophrenia: a preliminary study. Biol Psychiatry 2010, 68: 657-66.
14. Trixler M, Tényi T, Kosztolányi G. Minor Physical Anomalies and Chromosomal Fragility Schizophrenia. Preliminary Report Int J Hum Genet 2005, 5: 173-177. Markers in
15. Diez-Martin J, Hoenicka J, Martínez I et al. COMT Val158Met Polymorphism and schizophrenia in a series of Spanish patients. Med Clin (Barc) 2007, 128:41-4.
16. DeRosse P, Funke B, Burdick EK, Lencz T, Goldberg ET, Kane MJ, Kucherlapati R, Malhotra KA. COMT genotype and manic symptoms in schizpoprenia. Schizophrenia Research 2006, 87:28-31.
17. Ehlis AC, Reif A, Herrmann MJ, Lesch KP, Fallgatter AJ. Impact of catechol-O- methyltransferase on prefrontal brain functioning in schzophrenia spectrum disorders. Neuropsychopharmacology 2007, 32: 162-70.
18. Daniels JK, Williams NM, Williams J, Jones LA, Cordna AG, Murphy KC, Spurlock G, Riley G, Scamber P, Asherson P, McGuffin P, Owen MJ. No evidence for allelic association between schizophrenia and a polymorphism determining high or low catechol-O methyltransferase activity. Am J Psychiatry 1996, 153: 268-270
19. Herken H and Erdal ME. Cathecol-O- methyltransferase gene polymorphism in schizophrenia: evidence for association between symptamotology and prognosis. Psychiatr Genet 2001, 11(2): 105-109