Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, North Carolina, USA.
Alzheimers Dement. 2021 Nov;17(11):1779-1787. doi: 10.1002/alz.12413. Epub 2021 Jul 26.
Despite advances, understanding the protective role of the apolipoprotein E (APOE) ε2 allele in Alzheimer's disease (AD) remains elusive.
We examined associations of variants comprised of the TOMM40 rs8106922 and APOE rs405509, rs440446, and ε2-encoding rs7412 polymorphisms with AD in a sample of 2862 AD-affected and 169,516 AD-unaffected non-carriers of the ε4 allele.
Association of the ε2/ε3 heterozygote of men with AD is 38% (P = 1.65 × 10 ) more beneficial when it is accompanied by rs8106922 major allele homozygote and rs405509 and rs440446 heterozygotes than by rs8106922 heterozygote and rs405509 and rs440446 major allele homozygotes. No difference in the beneficial associations of these two most common ε2/ε3-bearing variants with AD was identified in women. The role of ε2/ε3 heterozygote may be affected by different immunomodulation functions of rs8106922, rs405509, and rs440446 variants in a sex-specific manner.
Combination of TOMM40 and APOE variants defines a more homogeneous AD-protective ε2/ε3-bearing profile in men.
尽管已有进展，但人们对载脂蛋白 E（APOE）ε2 等位基因在阿尔茨海默病（AD）中的保护作用仍不甚了解。
我们在一个由 2862 名 AD 患者和 169516 名非 ε4 等位基因携带者组成的样本中，研究了 TOMM40 rs8106922 和 APOE rs405509、rs440446 和 ε2 编码 rs7412 变异与 AD 的关联。
与 rs8106922 杂合子和 rs405509、rs440446 杂合子相比，男性中 ε2/ε3 杂合子与 AD 的关联更为有益，其优势比为 38%（P=1.65×10）。而与 rs8106922 杂合子和 rs405509、rs440446 纯合子相比，男性中 ε2/ε3 杂合子与 AD 的关联并无差异。在女性中，这两种最常见的 ε2/ε3 携带变体与 AD 的有益关联没有差异。rs8106922、rs405509 和 rs440446 变体的不同免疫调节功能可能以性别特异性的方式影响 ε2/ε3 杂合子的作用。
TOMM40 和 APOE 变体的组合在男性中定义了一个更同质的具有 AD 保护作用的 ε2/ε3 携带特征。
