Cachide Maria, Carvalho Liliana, Rosa Ilka Martins, Wiltfang Jens, Henriques Ana Gabriela, da Cruz E Silva Odete A B
Neurosciences and Signalling Group, Medical Sciences Department, Institute of Biomedicine - iBiMED, University of Aveiro, Aveiro, Portugal.
Department of Psychiatry and Psychotherapy, University Medical Centre Goettingen (UMG), Georg-August University, Goettingen, Germany.
Front Dement. 2022 Oct 28;1:1001113. doi: 10.3389/frdem.2022.1001113. eCollection 2022.
ε4 and are the two main genetic risk factors for sporadic Alzheimer's Disease (AD). Among several variants, the rs744373 is frequently associated with AD risk by contributing to tau pathology and poor cognitive performance. This study addressed the association of and rs744373 to specific characteristics in a Portuguese primary care-based study group, denoted pcb-Cohort. The study included 590 participants from five primary care health centers in the Aveiro district of Portugal. Individuals were evaluated and scored for cognitive and clinical characteristics, and blood samples were collected from the volunteers meeting the inclusion and exclusion criteria ( = 505). and genotypes were determined, and their association with cognitive characteristics and other diseases that might contribute to cognitive deficits, namely depression, hypertension, type 2 diabetes, dyslipidemia, osteoarticular diseases, gastrointestinal diseases, cardiovascular and respiratory diseases, was assessed. The diseases attributed to the study group were those previously diagnosed and confirmed by specialists. The results generated through multivariate analysis show that ε4 carriers significantly associated with poorer cognitive performance (OR = 2.527; = 0.031). Additionally, there was a significant risk of dyslipidemia for ε4 carriers (OR = 1.804; = 0.036), whereas rs744373 risk-allele carriers were at a significantly lower risk of having dyslipidemia (OR = 0.558; = 0.006). Correlations were evident for respiratory diseases in which ε4 showed a protective tendency (OR = 0.515; = 0.088), and had a significative protective profile (OR = 0.556; = 0.026). Not of statistical significance, ε2 showed a trend to protect against type 2 diabetes (OR = 0.342; = 0.093), in contrast rs744373 risk-allele carriers were more likely to exhibit the disease (OR = 1.491; = 0.099). The data here presented clearly show, for the first time, that the two top genetic risk factors for sporadic AD impact a similar group of common diseases, namely dyslipidemia, respiratory diseases, and type 2 diabetes.
ε4和[此处原文缺失相关内容]是散发性阿尔茨海默病（AD）的两个主要遗传风险因素。在多个[此处原文缺失相关内容]变体中，rs744373通过导致tau病理改变和认知功能不佳，常与AD风险相关。本研究在一个以葡萄牙初级保健为基础的研究组（称为pcb队列）中探讨了[此处原文缺失相关内容]和rs744373与特定特征的关联。该研究纳入了来自葡萄牙阿威罗地区五个初级保健健康中心的590名参与者。对个体进行认知和临床特征评估并评分，从符合纳入和排除标准的志愿者中采集血样（n = 505）。确定了[此处原文缺失相关内容]和[此处原文缺失相关内容]的基因型，并评估了它们与认知特征以及可能导致认知缺陷的其他疾病（即抑郁症、高血压、2型糖尿病、血脂异常、骨关节疾病、胃肠道疾病、心血管和呼吸系统疾病）的关联。研究组所患疾病为先前由专家诊断并确认的疾病。多变量分析产生的结果表明，ε4携带者与较差的认知表现显著相关（OR = 2.527；P = 0.031）。此外，ε4携带者患血脂异常的风险显著增加（OR = 1.804；P = 0.036），而rs744373风险等位基因携带者患血脂异常的风险显著降低（OR = 0.558；P = 0.006）。在呼吸系统疾病方面相关性明显，其中ε4显示出保护倾向（OR = 0.515；P = 0.088），[此处原文缺失相关内容]具有显著的保护作用（OR = 0.556；P = 0.026）。ε2对2型糖尿病有保护趋势但无统计学意义（OR = 0.342；P = 0.093），相反，rs744373风险等位基因携带者更易患该疾病（OR = 1.491；P = 0.099）。此处呈现的数据首次清楚地表明，散发性AD的两个主要遗传风险因素影响一组相似的常见疾病，即血脂异常、呼吸系统疾病和2型糖尿病。
