Khalili-Moghadam Fereshteh, Hosseini Nejad Javad, Badri Taleb, Sadeghi Morteza, Gharechahi Javad
Student Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Heliyon. 2024 Sep 6;10(18):e37556. doi: 10.1016/j.heliyon.2024.e37556. eCollection 2024 Sep 30.
the gene encodes a membrane metalloendopeptidase, known as neprilysin (NEP). There are no reports on the potential implications of gene polymorphisms on the risk of Alzheimer's disease (AD) in the Iranian population. In this study, we studied the potential association of two single nucleotide polymorphisms (SNPs), rs6797911 and rs3736187, in the gene and the risk of developing AD in an Iranian population.
This case-control study comprised 120 AD-diagnosed patients and 120 healthy individuals without any prior family history of AD. The patient and control groups were matched for major demographic and health characteristics. Genotyping was performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR).
All patients included in this study were assessed by an experienced neurologist to exclude cases with other forms of dementia based on a brain computed tomography scan and other clinical findings. There were no significant differences in demographic and health characteristics including sex, diabetes, blood pressure, and cigarette smoking status between case and control groups (p > 0.05). However, the age difference appeared significant. Both SNPs were significantly associated with the risk of AD in our study population. The rs3736187 (T > C, 3:155168489) was strongly associated with AD risk under the log-additive model (OR = 1.67, CI = 1.18-2.37, p-value = 0.003). The rs6797911 (T > A, 3:155144601) also showed a significant association with AD risk under the dominant model (TT vs. TA and AA, OR = 3.37, CI = 1.86-6.1, p-value <0.001).
There is a strong association between gene polymorphisms and susceptibility to AD in the Iranian population. Amyloid-β (Aβ) can serve as a substrate for the NEP metalloendopeptidase, the product of the gene. However, the mechanistic understanding of how these genetic variations affect NEP expression, function, and consequently susceptibility to AD, is poorly understood. Further research is required to fully understand the exact implication of gene variations on AD, particularly in a larger, ethnicity-diverse population.
该基因编码一种膜金属内肽酶，称为中性内肽酶（NEP）。关于该基因多态性对伊朗人群患阿尔茨海默病（AD）风险的潜在影响尚无相关报道。在本研究中，我们研究了该基因中的两个单核苷酸多态性（SNP），即rs6797911和rs3736187，与伊朗人群患AD风险之间的潜在关联。
这项病例对照研究包括120名经诊断患有AD的患者和120名无AD家族史的健康个体。患者组和对照组在主要人口统计学和健康特征方面进行了匹配。基因分型通过扩增阻滞突变系统 - 聚合酶链反应（ARMS-PCR）进行。
本研究纳入的所有患者均由经验丰富的神经科医生进行评估，根据脑部计算机断层扫描和其他临床发现排除患有其他形式痴呆的病例。病例组和对照组在包括性别、糖尿病、血压和吸烟状况等人口统计学和健康特征方面无显著差异（p>0.05）。然而，年龄差异似乎显著。在我们的研究人群中，这两个SNP均与AD风险显著相关。rs3736187（T>C，3:155168489）在对数加性模型下与AD风险密切相关（OR = 1.67，CI = 1.18 - 2.37，p值 = 0.003）。rs6797911（T>A，3:155144601）在显性模型下也显示出与AD风险显著相关（TT与TA和AA相比，OR = 3.37，CI = 1.86 - 6.1，p值<0.001）。
在伊朗人群中，该基因多态性与AD易感性之间存在密切关联。淀粉样β蛋白（Aβ）可作为该基因产物NEP金属内肽酶的底物。然而，对于这些基因变异如何影响NEP表达、功能以及进而影响AD易感性的机制理解尚少。需要进一步研究以充分了解该基因变异对AD的确切影响，特别是在更大规模、种族多样的人群中。
