血管危險因子基因Ninjurin2多型性與失智症之關聯性研究

Genetic Polymorphisms of Ninjurin2 Gene and the Risk of Dementia

林坤霈(Kun-Pei Lin)

指導教授 ： 程蘊菁

共同指導教授 ： 陳為堅(Wei-Jen Chen)

國立臺灣大學/公共衛生學院/流行病學研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.10108

摘要

背景
愈來愈多的證據顯示，血管危險因子，如高血壓，糖尿病，吸菸和高血脂症，可能與失智症的風險有關。然而，過去研究並無探討血管易感受基因Ninjurin2（NINJ2）的遺傳多型性與老年癡呆症風險之關係。本篇研究除了分析遺傳多型性 NINJ2基因與老年失智症風險相的關性，並同時探討NINJ2和其他血管危險因子之間的交互作用。
方法
從2007至2010年間，本研究自三家位於大台北地區的教學醫院招募了280位阿茲海默症和122血管性癡呆的患者。此外，在同一時期的時間，由健康檢查及在醫院服務的義工中招募了422位的健康對照組。本研究找出NINJ2基因中5個常見的（頻率> 5％） haplotype tagging 單核苷酸多型性，並研究NINJ2的序列變異之間和失智症的關聯。
結果
帶有NINJ2兩個變異同型合子(homozygous)者其阿茲海默症的風險較不帶有任何變異者低（rs11833579：OR = 0.44; 95％ CI = 0.24-0.81; rs12425791: OR = 0.39，95％ CI = 0.14-1.00）。此外，本研究找出五種常見的單體型(累積頻率, 97%; Global p = 0.03)，其中單體型CAGGA與阿茲海默症及血管型失智症有統計學上顯著的關聯。
結論
血管易感受基因NINJ2的遺傳多型性與阿茲海默症風險可能有關聯。

關鍵字

失智症 ； 阿茲海默症 ； NINJ2 ； 單核苷酸多型性 ； 單體型 ； 血管危險因子

並列摘要

Background
Accumulating evidences have showed that vascular risk factors, e.g., hypertension, diabetes mellitus and hyperlipidemia, may be related to the risk of dementia. This study investigated the association between genetic polymorphisms of a vascular susceptibility gene Ninjurin2 (NINJ2) and the risk of dementia, which has not been explored previously. The interactions between NINJ2 polymorphisms and other vascular risk factors on the risk of dementia were also explored.
Methods
A total of 280 Alzheimer’s disease (AD) patients and 122 vascular dementia (VaD) patients were recruited from three teaching hospitals from 2007 to 2010. Healthy controls (n = 422) from the health checkup clinics and volunteers at the hospitals were recruited during the same period of time. Five common (frequency > 5%) haplotype-tagging single nucleotide polymorphisms (htSNPs) in NINJ2 were genotyped to test for the association between sequence variants of NINJ2 and dementia.
Results
Homozygosity of two NINJ2 NPs was significantly associated with a decreased risk of AD [rs11833579: odds ratio (OR) = 0.44; 95% confidence interval (CI) = 0.24-0.81; rs12425791: OR = 0.39, 95% CI = 0.14-1.00]. Five common haplotypes (cumulative frequency, 97%) were observed. The global test for association between haplotypes and AD was significant (p = 0.03). Haplotype CAGGA was significantly associated with a decreased risk of AD (OR = 0.34, 95% CI = 0.12-0.94).
Conclusion
Inherited polymorphisms of the vascular susceptibility gene NINJ2 were associated with the risk of AD.

並列關鍵字

Dementia ； NINJ2 ； SNP ； haplotype ； vascular risk factor

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