Research Article
Çocukluk Çağı Akut Lenfoblastik Lösemili Hastalarda RFC G80A Polimorfizmi ve MTHFR Polimorfizmleri ile İlişkilendirilmesi
Abstract
Amaç:
Folat metabolik yolağı nükleotid sentezi ve DNA
metilasyonu için gerekli olduğundan lösemi gelişimde önemli rol oynamaktadır.
Folat eksikliği, DNA kırıklarına sebep olmaktadır. Bu yüzden folatla ilişkili
polimorfizmler, çocukluk çağı akut
lenfoblastik lösemisine (ALL) neden olabilmektedir. MTHFR (Metilentetrahidrofolat Redüktaz), DHFR (Dehidrofolat Redüktaz), CBS (Sistationin Beta Sentaz), TYMS (Timidilat
Sentaz) ve RFC (Reduces Factor Carrier-1) bulunan değişimler, folat seviyesi ve
DNA sentezini etkilediğinden dolayı, folat yolağında önemli role sahiptirler.
Bu çalışmadaki amacımız, folat metabolik yolağı ile ilişkili olan RFC ve MTHFR genlerdeki
polimorfizimlerin çocukluk çağı lösemisi üzerinde etkisi olup olmadığını
araştırmaktır.
Materyal ve Metod: Çalışmaya
Lösante Çocuk ve Yetişkin hastanesinde 103 akut lenfoblastik lösemi tanısı
almış çocuk hasta dâhil edildi. RFC geni G80A ve MTHFR geni polimorfizmleri genotipleme
işlemi RFLP (Restriction Fragment Length Polymorphism)
ve Real Time PCR yöntemleri ile gerçekleştirildi.
Bulgular:
Genotip ve allel frekanslarının sonuçlarına göre, hasta ve kontrol grubu
arasında herhangi bir istatistiksel farklılık görülmemiştir. RFC G80A ve MTHFR polimorfizmleri
birlikteliği, ANOVA testi ile yapılan analiz sonucu istatistiksel olarak
anlamlı bulunamamıştır (p> 0,05).
Sonuçlar
Çalışmamız, Türk çocukluk çağı ALL hastalarında, RFC ve
MTHFR polimorfizmlerle lösemi patogenezi arasındaki ilişkiyi tanımlayan ve
frekansını tespit eden ilk tarama sonuçları olmasından dolayı önemlidir.
References
- 1. Baslund B, Gregers J, Nielsen CH. Reduced folate carrier polymorphism determines methotrexate uptake by B cells and CD4+ T cells. Rheumatology 2008 ;47(4):451-3.
- 2. Kim YI. Folic acid supplementation and cancer risk: point. Cancer Epidemiol Biomarkers Prev 2008;17(9):2220-5.
- 3. Koppen IJ, Hermans FJ, Kaspers GJ. Folate related gene polymorphisms andsusceptibility to develop childhood acute lymphoblastic leukaemia. Br J Haematol 2010;148(1):3-14.
- 4. Rabab M Aly, Mona M Taalab, Hayam F Ghazy. MTHFR A1298C and C677T gene polymorphisms and susceptibility to chronic myeloid leukemia in Egypt. Int J Clin Exp Pathol 2014; 7: 2571–2578.
- 5. Aşlar D, Özdiler E, Altuğ AT, Taştan H. Determination of Methylenetetrahydrofolate Reductase (MTHFR) gene polymorphism in Turkish patients with nonsyndromic cleft lip and palate. Int J Pediatr Otorhinolaryngol 2013;77:1143-6.
- 6. Boccia S, Hung R, Ricciardi G, Gianfagna F, Ebert MP, Fang JY, Gao CM, GötzeT, Graziano F, Lacasaña-Navarro M, Lin D, López-Carrillo L, Qiao YL, Shen H,Stolzenberg-Solomon R, Takezaki T, Weng YR, Zhang FF, van Duijn CM, Boffetta P,Taioli E. Meta- and pooled analyses of the methylenetetrahydrofolate reductaseC677T and A1298C polymorphisms and gastric cancer risk: a huge-GSEC review. Am J Epidemiol 2008;167(5):505-16.
- 7. Chango A, Emery-Fillon N, de Courcy GP, Lambert D, Pfister M, Rosenblatt DS,Nicolas JP. A polymorphism (80G->A) in the reduced folate carrier gene and itsassociations with folate status and homocysteinemia. Mol Genet Metab 2000;70(4):310-5.
- 8. Clifford AJ, Rincon G, Owens JE, Medrano JF, Moshfegh AJ, Baer DJ, Novotny JA.Single nucleotide polymorphisms in CETP, SLC46A1, SLC19A1, CD36, BCMO1, APOA5,and ABCA1 are significant predictors of plasma HDL in healthy adults. Lipids Health Dis 2013 8;12:66.
- 9. Rajgopal A, Sierra EE, Zhao R, Goldman ID. Expression of the reduced folatecarrier SLC19A1 in IEC-6 cells results in two distinct transport activities. Am J Physiol Cell Physiol 2001;281(5):C1579-86.
- 10. Collin SM, Metcalfe C, Zuccolo L, Lewis SJ, Chen L, Cox A, Davis M, Lane JA,Donovan J, Smith GD, Neal DE, Hamdy FC, Gudmundsson J, Sulem P, Rafnar T,Benediktsdottir KR, Eeles RA, Guy M, Kote-Jarai Z; UK Genetic Prostate Cancer Study Group, Morrison J, Al Olama AA, Stefansson K, Easton DF, Martin RM.Association of folate-pathway gene polymorphisms with the risk of prostatecancer: a population-based nested case-control study, systematic review, and meta-analysis. Cancer Epidemiol Biomarkers Prev 2009;18(9):2528-39.
- 11. Karathanasis NV, Stiakaki E, Goulielmos GΝ, Kalmanti M. The effect of RFC G80A polymorphism in Cretan children with acute lymphoblastic leukemia and its interaction with MTHFR C677T and A1298C polymorphisms. Int J Lab Hematol. 2014;36(4):425-30.
- 12. Akin DF, Oner D, Sipahi K, Mumcuoglu M, Kurekci E, Ezer U, Akar N. Screening of polymorphisms in the folate pathway in Turkish pediatric Acute Lymphoblastic Leukemia patients. Egyptian Journal of Medical Human Genetics 2017: 18; 349-353.
- 13. Rocha JC, Cheng C, Liu W, Kishi S, Das S, Cook EH, Sandlund JT, Rubnitz J,Ribeiro R, Campana D, Pui CH, Evans WE, Relling MV. Pharmacogenetics of outcome in children with acute lymphoblastic leukemia. Blood 2005:15;105(12):4752-8.
- 14. Stanisławska-Sachadyn A, Mitchell LE, Woodside JV, Buckley PT, Kealey C, Young IS, Scott JM, Murray L, Boreham CA, McNulty H, Strain JJ, Whitehead AS. The reduced folate carrier (SLC19A1) c.80G>A polymorphism is associated with red cell folate concentrations among women. Ann Hum Genet 2009:73;484-91.
- 15. Coppedè F, Lorenzoni V, Migliore L. The reduced folate carrier (RFC-1) 80A>G polymorphism and maternal risk of having a child with Down syndrome: a meta-analysis. Nutrients 2013: 5;5(7):2551-63.
- 16. Li WJ, Jiang H, Fang XJ, Ye HL, Liu MH, Liu YW, Chen Q, Zhang L, Zhang JY,Yuan CL, Zhang QY. Polymorphisms in thymidylate synthase and reduced folat carrier (SLC19A1) genes predict survival outcome in advanced non-small cell lung cancer patients treated with pemetrexed-based chemotherapy. Oncol Lett 2013;5(4):1165-1170.
- 17. Lautner-Csorba O, Gézsi A, Erdélyi DJ, Hullám G, Antal P, Semsei ÁF, Kutszegi N, Kovács G, Falus A, Szalai C. Roles of genetic polymorphisms in the folate pathway in childhood acute lymphoblastic leukemia evaluated by Bayesian relevance and effect size analysis. PLoS One 2013:5;8(8):e69843.
- 18. Yates Z, Lucock M. G80A reduced folate carrier SNP modulates cellular uptake of folate and affords protection against thrombosis via a non homocysteine related mechanism. Life Sci 2005:14;77(22):2735-42.
- 19. Levy AS, Sather HN, Steinherz PG, Sowers R, La M, Moscow JA, Gaynon PS, Uckun FM, Bertino JR, Gorlick R; Children's Cancer Group Study. Reduced folate carrier and dihydrofolate reductase expression in acute lymphocytic leukemia may predict outcome: a Children's Cancer Group Study. J Pediatr Hematol Oncol 2003;25(9):688-95.
Year 2018,
Volume: 49 Issue: 2, 180 - 183, 27.06.2018
Abstract
References
- 1. Baslund B, Gregers J, Nielsen CH. Reduced folate carrier polymorphism determines methotrexate uptake by B cells and CD4+ T cells. Rheumatology 2008 ;47(4):451-3.
- 2. Kim YI. Folic acid supplementation and cancer risk: point. Cancer Epidemiol Biomarkers Prev 2008;17(9):2220-5.
- 3. Koppen IJ, Hermans FJ, Kaspers GJ. Folate related gene polymorphisms andsusceptibility to develop childhood acute lymphoblastic leukaemia. Br J Haematol 2010;148(1):3-14.
- 4. Rabab M Aly, Mona M Taalab, Hayam F Ghazy. MTHFR A1298C and C677T gene polymorphisms and susceptibility to chronic myeloid leukemia in Egypt. Int J Clin Exp Pathol 2014; 7: 2571–2578.
- 5. Aşlar D, Özdiler E, Altuğ AT, Taştan H. Determination of Methylenetetrahydrofolate Reductase (MTHFR) gene polymorphism in Turkish patients with nonsyndromic cleft lip and palate. Int J Pediatr Otorhinolaryngol 2013;77:1143-6.
- 6. Boccia S, Hung R, Ricciardi G, Gianfagna F, Ebert MP, Fang JY, Gao CM, GötzeT, Graziano F, Lacasaña-Navarro M, Lin D, López-Carrillo L, Qiao YL, Shen H,Stolzenberg-Solomon R, Takezaki T, Weng YR, Zhang FF, van Duijn CM, Boffetta P,Taioli E. Meta- and pooled analyses of the methylenetetrahydrofolate reductaseC677T and A1298C polymorphisms and gastric cancer risk: a huge-GSEC review. Am J Epidemiol 2008;167(5):505-16.
- 7. Chango A, Emery-Fillon N, de Courcy GP, Lambert D, Pfister M, Rosenblatt DS,Nicolas JP. A polymorphism (80G->A) in the reduced folate carrier gene and itsassociations with folate status and homocysteinemia. Mol Genet Metab 2000;70(4):310-5.
- 8. Clifford AJ, Rincon G, Owens JE, Medrano JF, Moshfegh AJ, Baer DJ, Novotny JA.Single nucleotide polymorphisms in CETP, SLC46A1, SLC19A1, CD36, BCMO1, APOA5,and ABCA1 are significant predictors of plasma HDL in healthy adults. Lipids Health Dis 2013 8;12:66.
- 9. Rajgopal A, Sierra EE, Zhao R, Goldman ID. Expression of the reduced folatecarrier SLC19A1 in IEC-6 cells results in two distinct transport activities. Am J Physiol Cell Physiol 2001;281(5):C1579-86.
- 10. Collin SM, Metcalfe C, Zuccolo L, Lewis SJ, Chen L, Cox A, Davis M, Lane JA,Donovan J, Smith GD, Neal DE, Hamdy FC, Gudmundsson J, Sulem P, Rafnar T,Benediktsdottir KR, Eeles RA, Guy M, Kote-Jarai Z; UK Genetic Prostate Cancer Study Group, Morrison J, Al Olama AA, Stefansson K, Easton DF, Martin RM.Association of folate-pathway gene polymorphisms with the risk of prostatecancer: a population-based nested case-control study, systematic review, and meta-analysis. Cancer Epidemiol Biomarkers Prev 2009;18(9):2528-39.
- 11. Karathanasis NV, Stiakaki E, Goulielmos GΝ, Kalmanti M. The effect of RFC G80A polymorphism in Cretan children with acute lymphoblastic leukemia and its interaction with MTHFR C677T and A1298C polymorphisms. Int J Lab Hematol. 2014;36(4):425-30.
- 12. Akin DF, Oner D, Sipahi K, Mumcuoglu M, Kurekci E, Ezer U, Akar N. Screening of polymorphisms in the folate pathway in Turkish pediatric Acute Lymphoblastic Leukemia patients. Egyptian Journal of Medical Human Genetics 2017: 18; 349-353.
- 13. Rocha JC, Cheng C, Liu W, Kishi S, Das S, Cook EH, Sandlund JT, Rubnitz J,Ribeiro R, Campana D, Pui CH, Evans WE, Relling MV. Pharmacogenetics of outcome in children with acute lymphoblastic leukemia. Blood 2005:15;105(12):4752-8.
- 14. Stanisławska-Sachadyn A, Mitchell LE, Woodside JV, Buckley PT, Kealey C, Young IS, Scott JM, Murray L, Boreham CA, McNulty H, Strain JJ, Whitehead AS. The reduced folate carrier (SLC19A1) c.80G>A polymorphism is associated with red cell folate concentrations among women. Ann Hum Genet 2009:73;484-91.
- 15. Coppedè F, Lorenzoni V, Migliore L. The reduced folate carrier (RFC-1) 80A>G polymorphism and maternal risk of having a child with Down syndrome: a meta-analysis. Nutrients 2013: 5;5(7):2551-63.
- 16. Li WJ, Jiang H, Fang XJ, Ye HL, Liu MH, Liu YW, Chen Q, Zhang L, Zhang JY,Yuan CL, Zhang QY. Polymorphisms in thymidylate synthase and reduced folat carrier (SLC19A1) genes predict survival outcome in advanced non-small cell lung cancer patients treated with pemetrexed-based chemotherapy. Oncol Lett 2013;5(4):1165-1170.
- 17. Lautner-Csorba O, Gézsi A, Erdélyi DJ, Hullám G, Antal P, Semsei ÁF, Kutszegi N, Kovács G, Falus A, Szalai C. Roles of genetic polymorphisms in the folate pathway in childhood acute lymphoblastic leukemia evaluated by Bayesian relevance and effect size analysis. PLoS One 2013:5;8(8):e69843.
- 18. Yates Z, Lucock M. G80A reduced folate carrier SNP modulates cellular uptake of folate and affords protection against thrombosis via a non homocysteine related mechanism. Life Sci 2005:14;77(22):2735-42.
- 19. Levy AS, Sather HN, Steinherz PG, Sowers R, La M, Moscow JA, Gaynon PS, Uckun FM, Bertino JR, Gorlick R; Children's Cancer Group Study. Reduced folate carrier and dihydrofolate reductase expression in acute lymphocytic leukemia may predict outcome: a Children's Cancer Group Study. J Pediatr Hematol Oncol 2003;25(9):688-95.
There are 19 citations in total.
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Original Research |
| Authors | |
| Publication Date | June 27, 2018 |
| Published in Issue | Year 2018 Volume: 49 Issue: 2 |
