Nadir Koçak, Filiz Özen, Malik Ejder Yıldırım, Öztürk Özdemir

Metilentetrahidrofolat Redüktaz (Mthfr) C677t ve A1298c Gen Polimorfizmleri

Amaç: Metilentetrahidrofolat redüktaz (MTHFR) folat metabolizmasının önemli bir enzimidir. İnsan MTHFR geni kromozom 1p36.3'de lokalizedir ve 563 amino asitten oluşan MTHFR enzimini kodlamaktadır. MTHFR geninde enzimin inaktivasyonu ile sonuçlanan bazı mutasyonlar kardiyovasküler ve serebrovasküler hastalıklar için önemli risk faktörleri olarak hiperhomosisteinemi ve homosistinüriye neden olur. Çok sayıdaki literatür verisine göre, MTHFR geninin polimorfik varyantları hiperhomosisteinemi, vasküler patolojiler, nöral tüp defektleri, demans, perinatal mortalite, mental bozukluklar, nörodejeneratif bozukluklar, migren ve kanser ile ilişikilidir. Bu çalışmanın amacı, MTHFR genindeki C677T ve A1298C polimorfizmlerinin allel frekansını saptamakdır. Bu amaçla, Sivas çevresinden rastgele seçilmiş 222 bireyde (109 erkek ve 113 kadın) MTHFR geninin C677T ve A1298C polimorfizmlerinin allel frekansı araştırıldı. Materyal ve Metod: Hasta grubunu Sivas bölgesinde ikamet eden bireyler arasında rastgele seçtik. 109 erkek ve 113 kadın olmak üzere toplam 222 kişi çalışmamıza dahil edildi. Çalışma grubunun bireyleri, çalışmanın amacı hakkında bilgilendirildi ve yazılı onam belgesi imzalatıldı. Çalışma grubuna aynı zamanda bir anket formu dolduruldu. Gen mutasyonlarını belirlemek için periferik kan örneklerinden DNA izolasyonu yapıldı. Mutasyon analizi revers hibridizasyon prensiplerine dayanan strip assay tekniğiyle yapıldı. Veriler SPSS 15.0 istatistik programı kullanılarak analiz edildi. Bulgular: 677 CT genotipinin Sivas çevresinde frekansı %54, 677 CC'nin %42 ve 677 TT'nin %4 olarak saptandı. Ayrıca, A1298C genotipinin Sivas çevresindeki frekansı %46, 1298 AA' nın %46 ve 1298 CC' nin %9' idi. MTHFR 677 T allelinin ve MTHFR 1298 C allelinin allel frekansları ise her ikisi için % 31'di. Anahtar Sözcükler: Metilentetrahidrofolat Redüktaz, Polimorfizm, Homosistein

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The C677t and A1298c Polymorphisms of Methylenetetrahydrofolate Reductase (Mthfr) Gene

Aim: Methylenetetrahydrofolate reductase is an important enzyme of folate metabolism. Human MTHFR gene is localized to chromosome 1p36.3 and coded MTHFR enzyme which consists of 563 amino acids. Some mutations seen in the MTHFR gene, resulting in the inactivation of the enzyme, cause hyperhomocysteinemia and homocystinuria as being important risk factors for cardiovascular and cerebrovascular diseases. According to the numerous literature data, polymorphic variant of the MTHFR-encoding gene, is associated with hyperhomocysteinemia, vascular pathologies, neural tube defects, dementia, perinatal mortality, mental disorders, neurodegenerative disorders, cancer and migraine. The aim of this study was to determine allelic frequencies of the polymorphic MTHFR gene C677T, A1298C. In this regard, we have investigated the allelic frequencies of C677T and A1298C polymorphisms of the MTHFR gene in 222 (109 females and 113 males) randomized individuals around Sivas. Materials and Methods: The study group was selected between individuals residing in Sivas. Total 222 subjects (109 men and 113 woman) were enrolled in the study. The subjects were informed of the purpose of the study and signed a written consent, which had previously been approved by the Ethical Committee. They also filled out questionnaire. DNA isolation was performed from peripheral blood samples such that thegene polymorphisms were determined. The mutation analysis was performed by StripAssay technique which is based on the Reverse-Hybridization principle automatically. Data were analyzed by SPSS 15.0 package program. Results:: The frequency in around Sivas of the C677T genotype was 54%; of C677C, 42%; and of T677T, 4%. The frequency in around Sivas of 1298 AC genotype was 46%; of A1298A, 46%; and of C1298C, 9%. The allelic frequencies of the T allele of MTHFR 677 and the C allele of MTHFR 1298 were both 31%. Key words: Methylenetetrahydrofolate Reductase, Polimorphism, Homocysteine

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