Kulminski Alexander M, Shu Leonardo, Loika Yury, He Liang, Nazarian Alireza, Arbeev Konstantin, Ukraintseva Svetlana, Yashin Anatoliy, Culminskaya Irina
Biodemography of Aging Research Unit Social Science Research Institute Duke University Durham North Carolina.
Alzheimers Dement (Amst). 2020 Feb 6;12(1):e12008. doi: 10.1002/dad2.12008. eCollection 2020.
Apolipoprotein E () ε2 and ε4 alleles encoded by rs7412 and rs429358 polymorphisms, respectively, are landmark contra and pro "risk" factors for Alzheimer's disease (AD).
We examined differences in linkage disequilibrium (LD) structures between (1) AD-affected and unaffected subjects and (2) older AD-unaffected and younger subjects in the 19q13.3 region harboring rs7412 and rs429358.
AD is associated with sex-nonspecific heterogeneous patterns of decreased and increased LD of rs7412 and rs429358, respectively, with other polymorphisms from five genes in this region in AD-affected subjects. The LD patterns in older AD-unaffected subjects resembled those in younger individuals. Polarization of the ε4- and ε2 allele-related heterogeneous LD clusters differentiated cell types and implicated specific tissues in AD pathogenesis.
Protection and predisposition to AD is characterized by an interplay of rs7412 and rs429358, with multiple polymorphisms in the 19q13.3 region in a tissue-specific manner, which is not driven by common evolutionary forces.
分别由rs7412和rs429358多态性编码的载脂蛋白E（）ε2和ε4等位基因，是阿尔茨海默病（AD）标志性的反向和正向“风险”因素。
我们研究了（1）AD患者与未患病者以及（2）19q13.3区域中年龄较大的未患AD者与年龄较小者之间连锁不平衡（LD）结构的差异，该区域包含rs7412和rs429358。
在AD患者中，AD与rs7412和rs429358的LD降低和升高的性别非特异性异质性模式相关，分别与该区域五个基因的其他多态性有关。年龄较大的未患AD者的LD模式与年龄较小者相似。与ε4和ε2等位基因相关的异质性LD簇的极化区分了细胞类型，并暗示了AD发病机制中的特定组织。
AD的保护和易感性特征在于rs7412和rs429358之间的相互作用，与19q13.3区域中的多个多态性以组织特异性方式相互作用，这不是由共同的进化力量驱动的。
