神經成長因子接受器基因多型性與阿茲海默症風險之關聯性研究

Abstract

背景：基底前腦的膽鹼性神經退化是阿茲海默症主要病徵之一。膽鹼性神經的減少可能歸因於神經成長因子接受器所引發的凋亡前訊號所導致。至今，只有一篇文獻探討神經成長因子接受器基因多型性( Nerve growth factor receptor, NGFR) 跟阿茲海默症之間的關係。 方法：此研究為病例對照研究。個案收集從2007年起至2010年，自北部三間教學醫院收集了278位阿茲海默症病人，422對照組來自臺大醫院健檢參與者及志工。本研究選取NGFR五個常見的 (frequency 5%) haplotype-tagging 單核苷酸多型性 (htSNPs)，以探討NGFR基因多型性與阿茲海默症之關係。 結果：調整年齡、性別及Apolipoprotein E (ApoE) 4對偶基因後，帶有rs734194一個或兩個變異的對偶基因者，其阿茲海默症的危險性較降低 [TG vs. TT: OR = 0.86，95% confidence interval (CI) = 0.59-1.24；GG vs. TT：OR = 0.45，95% CI = 0.26-0.95]。由五個htSNPs 共可組合成7 個單倍體型 (haplotype)。帶有一個或兩個變異的Haplotype GCGCG者相對於未帶者，其阿茲海默症的危險性相對減少。 (1 vs. 0變異：OR = 0.9，95% CI = 0.62-1.31；2 vs. 0變異：OR=0.39，95% CI = 0.17-0.88)。根據性別及ApoE 4分層後，阿茲海默症與NGFR沒有顯著相關性存在。 結論：在此亞洲族群中，NGFR的基因多型性對於阿茲海默症的風險扮演著重要的角色。

Background. Degeneration of basal forebrain cholinergic neurons (BFCN) is a characteristic of Alzheimer’s disease (AD). Loss of BFCN is attributable to the proapoptotic signaling induced by nerve growth factor receptor (NGFR). Only one study has investigated the association between NGFR polymorphisms and the risk of human AD. Methods. This case-control study recruited 278 AD patients from three teaching hospitals and 422 controls from Health Checkup Department and volunteers of the hospital in 2007 - 2010. Five common (frequency 5%) haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected from NGFR gene to test the association between sequence variants of NGFR and the risk of AD. Results. Either one copy or two copies of variant rs734194 was associated with a decreased risk of AD, respectively [TG vs. TT: odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.59-1.24; GG vs. TT: OR = 0.45, 95% CI = 0.26-0.95], after adjusting for age, sex and Apolipoprotein E (ApoE) 4 status. Seven common haplotypes were identified. Haplotype GCGCG was associated with a decreased risk of AD (1 vs. 0 copies: OR = 0.9, 95% CI = 0.62-1.31; two vs. 0 copies: OR = 0.39, 95%CI = 0.17-0.88). No significant association was observed for AD after stratification by sex and ApoE 4 status. Conclusion. The genetic polymorphisms of NGFR play a significant role on the risk of AD in this Asian population.