We investigated whether particular immunoglobulin GM ( 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 HLA-DRB1 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（标记）等位基因（单独或与已知的人类白细胞抗原 (HLA) 风险等位基因上位）是否与阿尔茨海默病 (AD) 的发展相关。

采用前瞻性队列研究设计，我们对 209 名非洲裔美国人 (AA) 和 638 名欧洲裔美国人 (EA) 参与者的 DNA 样本进行了 IgG1（GM 3 和 GM 17）、IgG2（GM 23+ 和 GM 23–）和 HLA- 基因分型。通过 TaqMan 和 rhAMP 基因分型分析检测DRB1 rs9271192 (A/C) 等位基因。

在 EA 受试者中，GM 或 HLA 等位基因（无论是单独的还是上位的）均与 AD 的发展时间无关。在 AA 受试者中，GM 和 HLA 等位基因单独与 AD 发展时间无关。然而，存在显着的相互作用：在存在 GM 3（即 GM 3/3 和 GM 3/17 受试者）的情况下，HLA-C 等位基因的存在与发生 4 倍的可能性增加相关。 AD 与不存在 AD 的比较（风险比 [HR] 4.17，95% CI，1.28–13.58）。然而，在缺乏 GM 3（GM 17/17 受试者）的情况下，HLA-C 等位基因的存在与 AD 发展时间无关（HR 1.10，95% CI，0.50-2.41）。

这些结果表明特定的 GM 和 HLA 等位基因上位性地促进 AD 的发展。