Pandey Janardan P, Nietert Paul J, Kothera Ronald T, Barnes Lisa L, Bennett David A
Department of Microbiology and Immunology (J.P.P., R.T.K.) and Department of Public Health, Sciences (P.J.N.), Medical University of South Carolina, Charleston; and Rush Alzheimer's Disease Center (L.L.B., D.A.B.), Rush University Medical Center, Chicago, IL.
Neurol Genet. 2021 Feb 16;7(2):e565. doi: 10.1212/NXG.0000000000000565. eCollection 2021 Apr.
We investigated whether particular immunoglobulin GM (γ marker) alleles-individually or epistatically with a known human leukocyte antigen (HLA) risk allele-were associated with the development of Alzheimer disease (AD).
Using a prospective cohort study design, we genotyped DNA samples from 209 African American (AA) and 638 European American (EA) participants for IgG1 (GM 3 and GM 17), IgG2 (GM 23+ and GM 23-), and rs9271192 (A/C) alleles by TaqMan and rhAMP genotyping assays.
In EA subjects, none of the GM or HLA alleles-individually or epistatically-were associated with time to development of AD. In AA subjects, GM and HLA alleles individually were not associated with time to development of AD. However, there was a significant interaction: In the presence of GM 3 (i.e., GM 3/3 and GM 3/17 subjects), the presence of the HLA-C allele was associated with a 4-fold increase in the likelihood of developing AD compared with its absence (hazard ratio [HR] 4.17, 95% CI, 1.28-13.58). In the absence of GM 3 (GM 17/17 subjects), however, the presence of the HLA-C allele was not associated with time to development of AD (HR 1.10, 95% CI, 0.50-2.41).
These results show that particular GM and HLA alleles epistatically contribute to the development of AD.
我们研究了特定的免疫球蛋白GM（γ标记）等位基因——单独或与已知的人类白细胞抗原（HLA）风险等位基因存在上位性相互作用时——是否与阿尔茨海默病（AD）的发生相关。
采用前瞻性队列研究设计，我们通过TaqMan和rhAMP基因分型检测法，对209名非裔美国人（AA）和638名欧裔美国人（EA）参与者的DNA样本进行IgG1（GM 3和GM 17）、IgG2（GM 23 +和GM 23 -）以及rs9271192（A/C）等位基因的基因分型。
在EA受试者中，GM或HLA等位基因单独或存在上位性相互作用时，均与AD发病时间无关。在AA受试者中，GM和HLA等位基因单独与AD发病时间无关。然而，存在显著的相互作用：在存在GM 3的情况下（即GM 3/3和GM 3/17受试者），与不存在HLA - C等位基因相比，存在该等位基因会使患AD的可能性增加4倍（风险比[HR] 4.17，95%置信区间，1.28 - 13.58）。然而，在不存在GM 3的情况下（GM 17/17受试者），HLA - C等位基因的存在与AD发病时间无关（HR 1.10，95%置信区间，0.50 - 2.41）。
这些结果表明，特定的GM和HLA等位基因通过上位性相互作用促进AD的发生。
