Institute of Immunology, Faculty of Medicine, Comenius University in Bratislava, 81108 Bratislava, Slovakia.
Medirex Group Academy, Ltd, 82016 Bratislava, Slovakia.
J Integr Neurosci. 2022 Jun 1;21(4):105. doi: 10.31083/j.jin2104105.
Triggering receptor expressed on myeloid cells 2 (TREM2) is an important modulator of innate immune responses. In the human brain, TREM2 is primarily expressed on microglia and is involved in cell survival, phagocytosis, and regulation of inflammation. TREM2 dysfunction has been linked to the pathogenesis of various neurodegenerative diseases including Alzheimer's disease (AD). Rare coding variants of the gene have been reported to modulate AD risk in several populations, however, data on their association with susceptibility to AD in the Slovak population have been missing.
We have analyzed 10 non-synonymous coding variants located in exon 2 by direct sequencing in 270 late-onset Alzheimer's disease (LOAD) patients and 331 controls.
Four out of 10 mutant variants have been identified in the analyzed groups, namely rs75932628 C > T (R47H), rs142232675 C > T (D87N), rs143332484 C > T (R62H), and rs2234253 G > T (T96K). R47H was found only in the AD group, while T96K was present only in the controls. Although no significant association between coding variants and LOAD susceptibility has been detected, the observed odds ratio (OR) of 3.69 for R47H carriers suggests an increased risk of LOAD for this variant in the Slovak population. Moreover, we also found a higher OR for the rs143332484-T allele in ε4 non-carriers (1.99) when compared to ε4 carriers (0.62).
Our results suggest an impact of specific rare coding variants on AD risk in the Slovak population.
髓系细胞触发受体 2（TREM2）是先天免疫反应的重要调节剂。在人类大脑中，TREM2 主要表达于小胶质细胞，参与细胞存活、吞噬作用和炎症调节。TREM2 功能障碍与包括阿尔茨海默病（AD）在内的各种神经退行性疾病的发病机制有关。已有研究报道，基因的罕见编码变异可调节多个群体的 AD 发病风险，但斯洛伐克人群中这些变异与 AD 易感性的关联数据尚缺乏。
我们通过直接测序分析了 270 例迟发性 AD（LOAD）患者和 331 例对照者中位于外显子 2 的 10 个非同义编码变异。
在所分析的两组中，共发现了 4 个突变变异，即 rs75932628C>T（R47H）、rs142232675C>T（D87N）、rs143332484C>T（R62H）和 rs2234253G>T（T96K）。R47H 仅存在于 AD 组，而 T96K 仅存在于对照组。虽然未检测到编码变异与 LOAD 易感性之间存在显著关联，但 R47H 携带者的观察比值比（OR）为 3.69，提示该变异在斯洛伐克人群中增加了 LOAD 的风险。此外，与 ε4 携带者（0.62）相比，我们还发现 ε4 非携带者中 rs143332484-T 等位基因的 OR 更高（1.99）。
我们的研究结果表明，特定的 罕见编码变异可能对斯洛伐克人群的 AD 风险产生影响。
