CD33 rs3865444:C>A single nucleotide polymorphism (SNP) has been previously associated with the risk of late‐onset Alzheimer's disease (LOAD); however, the results have been inconsistent across different populations. CD33 is a transmembrane receptor that plays an important role in AD pathogenesis by inhibiting amyloid β42 uptake by microglial cells. In this study, we aimed to validate the association between rs3865444 and LOAD risk in the Slovak population and to evaluate whether it was affected by the carrier status of the major LOAD risk allele apolipoprotein (APOE) ε4. CD33 rs3865444 and APOE variants were genotyped in 206 LOAD patients and 487 control subjects using the polymerase chain reaction–restriction fragment length polymorphism method and direct sequencing, respectively. Logistic regression analysis revealed a significant association of rs3865444 A allele with a reduced LOAD risk that was only present in APOE ε4 allele carriers (AA + CA versus CC: p = .0085; OR = 0.45; 95% CI = 0.25‒0.82). On the other hand, no such association was found in subjects without the APOE ε4 (p = .75; OR = 0.93; 95% CI = 0.61‒1.42). Moreover, regression analysis detected a significant interaction between CD33 rs3865444 A and APOE ε4 alleles (p = .021 for APOE ε4 allele dosage and p = .051 for APOE ε4 carriage status), with synergy factor (SF) value of 0.49 indicating an antagonistic effect between the two alleles in LOAD risk. In conclusion, our results suggest that CD33 rs3865444:C˃A substitution may reduce the risk of LOAD in Slovaks by antagonizing the effect conferred by the major susceptibility allele APOE ε4.

中文翻译：

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CD33 rs3865444:C˃A 多态性与斯洛伐克人迟发性阿尔茨海默病风险降低的关联仅限于携带 APOE ε4 等位基因的受试者

CD33 rs3865444:C>单核苷酸多态性 (SNP) 先前已与晚发性阿尔茨海默病 (LOAD) 的风险相关；然而，不同人群的结果不一致。CD33 是一种跨膜受体，通过抑制小胶质细胞对淀粉样蛋白 β42 的摄取，在 AD 发病机制中起重要作用。在本研究中，我们旨在验证 rs3865444 与斯洛伐克人群中 LOAD 风险之间的关联，并评估其是否受主要 LOAD 风险等位基因载脂蛋白 (APOE) ε4 携带者状态的影响。CD33 rs3865444 和 APOE 变体分别使用聚合酶链反应限制性片段长度多态性方法和直接测序在 206 名 LOAD 患者和 487 名对照受试者中进行基因分型。Logistic 回归分析显示 rs3865444 A 等位基因与降低的 LOAD 风险显着相关，仅存在于 APOE ε4 等位基因携带者中（AA + CA 与 CC：p = .0085；OR = 0.45；95% CI = 0.25-0.82）。另一方面，在没有 APOE ε4 的受试者中没有发现这种关联（p = .75；OR = 0.93；95% CI = 0.61-1.42）。此外，回归分析检测到 CD33 rs3865444 A 和 APOE ε4 等位基因之间存在显着的相互作用（APOE ε4 等位基因剂量 p = .021，APOE ε4 携带状态 p = .051），协同因子 (SF) 值为 0.49，表明存在拮抗作用LOAD 风险中两个等位基因之间的影响。总之，我们的结果表明，CD33 rs3865444:C˃A 替代可能通过拮抗主要易感性等位基因 APOE ε4 赋予的作用来降低斯洛伐克人的 LOAD 风险。