The Role of Crucial Biochemical Parameters and Key Gene Polymorphisms in the One-Carbon Pathway in Parkinson's Disease: Case-Control Study
Tek Karbon Yolağındaki Önemli Biyokimyasal Parametrelerin ve Gen Polimorfizmlerinin Parkinson Hastalığındaki Rolü: Olgu Kontrol Çalışması
J Lit Pharm Sci. 2024;13(3):141-50
doi: 10.5336/pharmsci.2024-102989
Makale Dili: EN
Tam Metin
ABSTRACT
Objective: Parkinson's disease (PD) is the second most common neurodegenerative disease. The cause of PD is shown to be the decrease or degradation of dopaminergic activity in the brainstem region, which is thought to be triggered by environmental factors, aging, infectious agents, and other pathological conditions. Abnormalities in the folate-mediated one-carbon pathway may play a role in the pathophysiology of PD as it increases total homocysteine (Hcy) levels. We aimed to show possible associations between folate, Hcy, cysteine (Cys), and vitamin B12 levels, which function in the one-carbon pathway, and PD risk. Furthermore, the effect of genetic polymorphism of MTHFR and MTR, which are involved in the one-carbon pathway, on PD risk was investigated. Material and Methods: 108 patients diagnosed with PD and 97 healthy volunteers participated in this study. The biochemical parameters were measured by ELISA, and genetic polymorphisms analyzed by polymerase chain reaction-restriction fragment length polymorphism. Results: After adjustment for confounding factors such as age, smoking habit, and gender, there was a statistically significant increase in the risk of PD as folic acid levels increased and as vitamin B12 and Hcy levels decreased. These findings suggest that extra folic acid intake in the patients' diets may have been the cause of these findings. Higher Hcy levels were observed in PD patients with the MTHFR C677T TT genotype and the MTR A2756G GG genotype. However, this difference was not significant. No effect of Cys levels on PD risk was observed. Conclusion: MTHFR C677T and MTR A2756G gene polymorphisms were not found to be risk factors for PD.
Keywords: Folic acid; genetic polymorphism; homocysteine; one-carbon group transferases; Parkinson's disease
Objective: Parkinson's disease (PD) is the second most common neurodegenerative disease. The cause of PD is shown to be the decrease or degradation of dopaminergic activity in the brainstem region, which is thought to be triggered by environmental factors, aging, infectious agents, and other pathological conditions. Abnormalities in the folate-mediated one-carbon pathway may play a role in the pathophysiology of PD as it increases total homocysteine (Hcy) levels. We aimed to show possible associations between folate, Hcy, cysteine (Cys), and vitamin B12 levels, which function in the one-carbon pathway, and PD risk. Furthermore, the effect of genetic polymorphism of MTHFR and MTR, which are involved in the one-carbon pathway, on PD risk was investigated. Material and Methods: 108 patients diagnosed with PD and 97 healthy volunteers participated in this study. The biochemical parameters were measured by ELISA, and genetic polymorphisms analyzed by polymerase chain reaction-restriction fragment length polymorphism. Results: After adjustment for confounding factors such as age, smoking habit, and gender, there was a statistically significant increase in the risk of PD as folic acid levels increased and as vitamin B12 and Hcy levels decreased. These findings suggest that extra folic acid intake in the patients' diets may have been the cause of these findings. Higher Hcy levels were observed in PD patients with the MTHFR C677T TT genotype and the MTR A2756G GG genotype. However, this difference was not significant. No effect of Cys levels on PD risk was observed. Conclusion: MTHFR C677T and MTR A2756G gene polymorphisms were not found to be risk factors for PD.
Keywords: Folic acid; genetic polymorphism; homocysteine; one-carbon group transferases; Parkinson's disease
ÖZET
Amaç: Parkinson hastalığı (PH) en yaygın ikinci nörodejeneratif hastalıktır. PH'nin nedeni, çevresel faktörler, yaşlanma, enfeksiyöz ajanlar ve diğer patolojik koşullar tarafından tetiklendiği düşünülen beyin sapı bölgesindeki dopaminerjik aktivitenin azalması veya bozulması olarak gösterilmektedir. Folat aracılı tek karbon yolağındaki anormallikler, toplam homosistein [homocysteine (Hcy)] seviyelerini artırdığı için PH patofizyolojisinde rol oynayabilir. Tek karbon yolağında işlev gören folat, Hcy, sistein [cysteine (Cys)] ve vitamin B12 düzeyleri ile PH riski arasındaki olası ilişkileri göstermeyi amaçladık. Ayrıca, tek karbon yolunda yer alan MTHFR ve MTR genetik polimorfizminin PH riski üzerindeki etkisi araştırılmıştır. Gereç ve Yöntemler: Bu çalışmaya 108 PH tanısı almış hasta ve 97 sağlıklı gönüllü katılmıştır. Biyokimyasal parametreler ELISA ile ölçülmüş ve genetik polimorfizmler polimeraz zincir reaksiyonu-restriksiyon parça uzunluk polimorfizmi ile analiz edilmiştir. Bulgular: Yaş, sigara alışkanlığı ve cinsiyet gibi karıştırıcı faktörler ayarlandıktan sonra, artan folik asit seviyeleri ve azalan B12 vitamini ve Hcy seviyeleri ile PH riski istatistiksel olarak anlamlı şekilde artmıştır. Bu bulgular, hastaların diyetlerinde fazladan folik asit alımının bu bulgulara neden olmuş olabileceğini düşündürmektedir. MTHFR C677T TT genotipine ve MTR A2756G GG genotipine sahip PH hastalarında daha yüksek Hcy seviyeleri gözlenmiştir. Ancak bu fark anlamlı bulunmamıştır. Cys düzeylerinin PH riski üzerinde etkisi gözlenmemiştir. Sonuç: MTHFR C677T ve MTR A2756G gen polimorfizmleri PH için risk faktörü olarak bulunmamıştır.
Anahtar Kelimeler: Folik asit; genetik polimorfizm; homosistein; tek karbon grup transferazlar; Parkinson hastalığı
Amaç: Parkinson hastalığı (PH) en yaygın ikinci nörodejeneratif hastalıktır. PH'nin nedeni, çevresel faktörler, yaşlanma, enfeksiyöz ajanlar ve diğer patolojik koşullar tarafından tetiklendiği düşünülen beyin sapı bölgesindeki dopaminerjik aktivitenin azalması veya bozulması olarak gösterilmektedir. Folat aracılı tek karbon yolağındaki anormallikler, toplam homosistein [homocysteine (Hcy)] seviyelerini artırdığı için PH patofizyolojisinde rol oynayabilir. Tek karbon yolağında işlev gören folat, Hcy, sistein [cysteine (Cys)] ve vitamin B12 düzeyleri ile PH riski arasındaki olası ilişkileri göstermeyi amaçladık. Ayrıca, tek karbon yolunda yer alan MTHFR ve MTR genetik polimorfizminin PH riski üzerindeki etkisi araştırılmıştır. Gereç ve Yöntemler: Bu çalışmaya 108 PH tanısı almış hasta ve 97 sağlıklı gönüllü katılmıştır. Biyokimyasal parametreler ELISA ile ölçülmüş ve genetik polimorfizmler polimeraz zincir reaksiyonu-restriksiyon parça uzunluk polimorfizmi ile analiz edilmiştir. Bulgular: Yaş, sigara alışkanlığı ve cinsiyet gibi karıştırıcı faktörler ayarlandıktan sonra, artan folik asit seviyeleri ve azalan B12 vitamini ve Hcy seviyeleri ile PH riski istatistiksel olarak anlamlı şekilde artmıştır. Bu bulgular, hastaların diyetlerinde fazladan folik asit alımının bu bulgulara neden olmuş olabileceğini düşündürmektedir. MTHFR C677T TT genotipine ve MTR A2756G GG genotipine sahip PH hastalarında daha yüksek Hcy seviyeleri gözlenmiştir. Ancak bu fark anlamlı bulunmamıştır. Cys düzeylerinin PH riski üzerinde etkisi gözlenmemiştir. Sonuç: MTHFR C677T ve MTR A2756G gen polimorfizmleri PH için risk faktörü olarak bulunmamıştır.
Anahtar Kelimeler: Folik asit; genetik polimorfizm; homosistein; tek karbon grup transferazlar; Parkinson hastalığı
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