Association Between Alzheimer Disease and APOE Gene Polymorphisms in Turkish Population

Öz

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common form of the dementia which is characterized by the accumulation of amyloid plaques at the extracellular compartment and formation of neurofibriller tangles at the intracellular compartment which results in the degeneration of the neuron bodies and synapses. APOE gene polymorphisms in late-onset AD have a significant effect on cellular levels and also have been associated with neuropathological conditions. To determine the effect of APOE gene polymorphisms on Alzheimer's patients, we have included 629 AD patients between 45-90 years and 200 healthy subjects into the study. APOE gene isoforms were determined by real-time PCR method. APOE genotype distributions were significantly different between the patient and control groups (p <0.001). There was a statistically significant difference in allele frequencies between patient and control groups (p <0.001). At ε4 allele carriers there was a 5.49 times higher risk of AD than the subjects that lack the ε4 allele (OR= 5.49, %95 CI: 3.86-7.81,  p<0.001). The MMSE (Mini-Mental State Examination) score was lower among APOE ε4-carriers when compared to the non-carriers (p<0.001). On the basis of all these data it can be concluded that the APOE ε4 allele increases the risk of development of AD. Our results confirmed that the APOE genotype is a risk factor for AD. However, considering the importance of the geographic location and ethnicity, it is a fact that larger molecular studies are needed to clearly determine the contribution of the APOE gene to the development of AD.

Anahtar Kelimeler

• Alzheimer Diseas,APOE,polymorphism

Türk Popülasyonunda APOE Polimorfizmleri ve Alzheimer Hastalığı Arasındaki İlişki

Öz

Alzheimer Hastalığı (AH), demansın en yaygın nedeni olan, sinaps ve nöronların kaybının yanı sıra hücre dışı amyloid plakların ve hücre içi nörofibriler yapıların patolojik oluşumları ile karakterize, en sık görülen progresif nörodejeneratif bir hastalıktır. Geç başlangıçlı AH’da Apolipoprotein E (APOE) gen polimorfizmleri hücresel seviyelerde önemli bir etkiye sahip olmakla beraber aynı zamanda nöropatolojik koşullarla da ilişkilendirilmiştir. APOE gen polimorfizmlerinin AH' ları üzerinde etkisini saptamak amacıyla yaptığımız çalışmamıza 45-90 yaş arasında olan 629 hasta ve 200 sağlıklı birey dahil edilmiştir. APOE geni izoformları gerçek zamanlı polimeraz zincir reaksiyonu (GZ-PZR) yöntemi ile incelenmiştir. Hasta ve kontrol grupları arasında hem APOE genotip dağılımları (p<0.001) hemde allel frekansları (p<0.001) açısından istatistiksel olarak anlamlı farklar tespit edilmiştir. APOE ε4 allel taşıyıcısı olan bireylerde ε4 alleli taşımayan bireylere göre AH riskinin 5.49 kat fazla olduğu sonucuna ulaşılmıştır (OR= 5.49, %95 CI: 3.86-7.81,  p<0.001). MMSE (Mini-Mental Durum Muayenesi) skorunun; ε4 alleli taşıyıcılarında, taşıyıcı olmayanlara göre daha düşük olduğu tespit edilmiştir (p<0.001). Bütün bu verilere dayanarak APOE 𝜀4 allelinin AH’nın gelişim riskini arttırdığı sonucuna varılabilir. Sonuçlarımız APOE genotipinin AH için bir risk faktörü olduğunu doğrulamıştır. APOE'nin AH gelişimine katkısını net olarak saptayabilmek için,  coğrafi konumun ve etnik kökenin önemi de dikkate alınarak, daha geniş çaplı moleküler çalışmalara ihtiyaç olduğu bir gerçektir.

Anahtar Kelimeler

• : Alzheimer Hastalığı,APOE,polimorfizm,ε4 allel

Kaynakça

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