ANALYSIS OF FACTOR V AND MTHFR GENES AS RISK FACTORS CONSTITUTING SUSCEPTIBILITY TO NEURAL TUBE DEFECTS: A CASE-CONTROL STUDY FROM TURKEY

Öz

Objective: This study targeted to bring a molecular perspective to occult neural tube defects and thus develop future preventive personalized medicine strategies. The roles of three genetic variations namely Factor V Leiden (FVL) (rs6025), MTHFR A1298C (rs1801131), and MTHFR C677T (rs1801133) were investigated in a Turkish cohort including both the mothers and children to better analyze the potential inherited effects of these variations.

Material and Methods: Children affected with neural tube defects (NTDs) and control children without NTDs were included in the study together with their mothers. DNA extractions were performed from collected blood samples with standard salting-out procedure. Isolated DNAs were genotyped with Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method.

Results: In terms of Factor V Leiden (FVL) (rs6025) in NTD risk, there was no statistically important association between mothers with NTDs-affected children and control group mothers (p=0.639). However, a statistically significant association was observed when NTDs-affected children were compared with the ones not affected (p=0.0144). There was a statistically important association of MTHFR A1298C (rs1801131) both in mothers comparisons and comparison between NTDs-affected children and not-affected children (respectively, p=0.005; 0.008). MTHFR C677T (rs1801133) genotypes and/or alleles did not act as risk factors for NTD development neither in mothers nor in children in this study (p˃0.05).

Conclusion: Our study indicates FVL mutation as an increased risk factor for NTD development, independently from the genotypes of mothers. MTHFR A1298C (rs1801131) homozygous AA genotype and A allele elevated the risk of NTD development both in mothers and children referring to the inherited role of this variation in Turkish population. However, MTHFR C677T (rs1801133) variation can not be considered as a risk factor in NTD development in our population.

Anahtar Kelimeler

• Neural tube defects (NTDs),genetic association,risk factors,, Factor V Leiden,5-10-methylenetetrahydrofolate reductase (MTHFR)

Nöral Tüp Defektlerinde Duyarlılık Oluşturan Risk Faktörleri Olarak Faktör V ve MTHFR Genlerinin Analizi: Türkiye'den Bir Vaka-Kontrol Çalışması

Öz

Amaç: Bu çalışma konjenital olmayan nöral tüp defektlerine moleküler bir perspektif sunmayı ve geleceğe yönelik önleyici bireyselleştirilmiş tıp stratejileri geliştirmeyi hedeflemiştir. Üç genetik varyasyon; Factor V Leiden (FVL) (rs6025), MTHFR A1298C (rs1801131) ve MTHFR C677T (rs1801133) bu varyasyonların potansiyel kalıtımsal etkilerini daha iyi analiz etmek için hem anneleri hem de çocukları içeren bir Türk kohortunda araştırılmıştır.

Gereç ve Yöntemler: Nöral tüp defektli (NTD) çocuklar ve NTD'li olmayan kontrol grubu çocukları anneleriyle beraber çalışmaya dahil edilmiştir. Toplanılan kan örneklerinden standart tuzla çöktürme prosedürüyle DNA ekstraksiyonları gerçekleştirilmiştir. İzole edilen DNA'lar Polimeraz Zincir Reaksiyonu-Restriksiyon Fragment Uzunluk Polimorfizmi (PCR-RFLP) metoduyla genotiplendirilmiştir.

Bulgular: Factor V Leiden (FVL) (rs6025) mutasyonunun NTD riskini arttırması açısından NTD'li çocuğa sahip annelerle kontrol grubu anneleri arasında istatistiksel olarak önemli bir ilişki mevcut değildir (p=0.639). Ancak, NTD'li çocuklarla etkilenmemiş çocuklar karşılaştırıldığı zaman istatistiksel olarak önemli bir ilişki gözlenmiştir (p=0.0144). MTHFR A1298C (rs1801131) açısından ise hem annelerin kendi aralarındaki karşılaştırmada hem de NTD'li çocuklar ve etkilenmemiş çocuklar arasında istatistiksel olarak önemli bir ilişki mevcuttur (sırasıyla p=0.005; 0.008). MTHFR C677T (rs1801133) genotipleri ve/veya allelleri ise bu çalışmada ne annelerde ne de çocuklarda NTD gelişimi açısından risk faktörü olarak rol oynamadığı görülmüştür (p˃0.05).

Sonuç: Çalışmamız, NTD gelişimi açısından FVL mutasyonunun annelerin genotiplerinden bağımsız olarak artmış bir risk faktörü olduğuna işaret etmektedir. MTHFR A1298C (rs1801131) homozigot AA genotipi ve A alleli bu varyasyonun Türk popülasyonunda kalıtımsal etkisine de vurgu yapacak şekilde hem annelerde hem de çocuklarda NTD gelişimi riskinde artışa yol açmaktadır. Ancak, MTHFR C677T (rs1801133) varyasyonu populasyonumuzda NTD gelişimi açısından bir risk faktörü olarak dikkate alınamamaktadır.

Anahtar Kelimeler

• Factor V Leiden,Nöral tüp defektleri,genetik assosiasyon,risk faktörleri,5-10-methylenetetrahydrofolate reductase (MTHFR)

Kaynakça

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