Alzheimer Hastalarında PSEN1 Geni Kodlayan Bölgelerinde ve APP Geni 16-17. Ekzonlarında Mutasyon Taraması ve APOE Genotiplendirmesi

Öz

Bu çalışmanın amacı, Alzheimer hastalarında (AD) presenilin-1 (PSEN1) geninin tüm ekzonları ve amiloid precursor protein (APP) geni 16-17. ekzonlarında mutasyon taraması gerçekleştirmek ve hastaların apolipoprotein-E (APOE) genotipini belirlemektir. PSEN1 geni tüm ekzonları ve APP geni 16-17.ekzonları, DSM-IV kriterlerine göre teşhis edilen 30 geç başlangıçlı Alzheimer hastası bireyde (GBAH) ve 40 demans tanısı bulunmayan kontrol bireyde DNA dizi analizi ile taranmıştır. Εk olarak, APOE genine ait ε2, ε3 ve ε4 polimorfizmlerinin genotip ve allel frekansları her iki grupta PZR-RFLP methodu kullanılarak belirlenmiştir. PSEN1 geni kodlayan bölgelerinde ve APP geni 16-17.ekzonlarında herhangi bir mutasyona rastlanılamamıştır. Ancak 26 hastada PSEN1 geni intron 8 bölgesinde rs165932 (G/T) polimorfizmi tespit edilmiştir. Bununla birlikte intronik polimorfizmin, genotip ve allel frekansları açısından kontrol ve hasta grupları arasında anlamlı bir fark bulunamamıştır (p>0.05). APOE ε3/ε4 genotipi hasta grubunda önemli derecede yüksek oranda iken (p<0.05) ε4 alel frekansı GBAH olgularında anlamlı derecede yüksek bulunmuştur. Hasta grubunda PSEN1 genotip dağılımı ve ε4 alel frekansı birlikte değerlendirildiğinde anlamlı bir ilişki bulunamamıştır (p>0.05). Çalışmamızda, GBAH ve ε4 alel frekansı arasında önemli bir ilişki olduğu belirlenirken, PSEN1 geni rs165932 (G/T) polimorfizmi ve hastalık patogenezi arasında herhangi bir ilişki bulunamamıştır.

Anahtar Kelimeler

• Alzheimer hastalığı,polimorfizm,mutasyon,PSEN1,APP,APOE

Screening For Mutations In The Coding Regions Of PSEN1 Gene, 16-17 Exons Of APP Gene And APOE Genotyping In Patients With Alzheimer’s Disease

Abstract

The aim of this study is to screen for mutations in the presenilin-1 (PSEN1) gene,16-17 exons of amyloid precursor protein (APP) gene and determining apolipoprotein-E (APOE) genotype in patients with Alzheimer’s disease (AD). The coding regions of PSEN1 gene, 16-17 exons of APP gene were screened by using DNA sequence analysis in 30 patients with late onset of Alzheimer’s disease (LOAD) diagnosed based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria and 40 non-dementia controls. Additionally, genotype and allele frequencies of ε2, ε3 and ε4 polymorphisms of APOE gene were determined by using PCR-RFLP methods in both groups. No mutation was found in the coding regions of PSEN1 gene and 16-17 exons of APP gene. On the other hand, rs165932 (G/T) polymorphism was found in intron 8 of PSEN1 in 26 patients. There was no significant difference in genotype and allele frequencies of intronic polymorphism between control group and patients (p>0.05). The frequency of ε3/ε4 genotype was significantly higher in patient group (p<0.05) and frequencies of ε4 allele were also significantly higher among the patients with LOAD (p<0.05). When PSEN1 genotype distribution and ε4 allele frequency were evaluated together in the patient group, no significant relation was found (p>0.05). We suggested that there was a potential association between LOAD and APOE ε4 allele; however, no result could found to link the between PSEN1 gene polymorphism and disease pathogenesis.

Keywords

• Alzheimer’s disease, polymorphism, mutation,PSEN1,APP,APOE

Kaynakça

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