Department of Molecular and Translational Medicine, University of Brescia, 25123, Brescia, Italy.
Clinical Chemistry Laboratory, Cytogenetics and Molecular Genetics Section, Diagnostic Department, ASST Spedali Civili Di Brescia, 25123, Brescia, Italy.
Metab Brain Dis. 2022 Jun;37(5):1569-1583. doi: 10.1007/s11011-022-00975-w. Epub 2022 Mar 30.
Cognitive decline of aging is modulated by chronic inflammation and comorbidities. In people with HIV-infection (PWH) it may also be affected by HIV-induced inflammation, lifestyle and long-term effects of antiretroviral therapies (ART). The role of genetics in the susceptibility to HIV-associated neurocognitive disorders (HAND) is not fully understood. Here we explored the possible relations among variants in 3 genes involved in inflammation and neurodegenerative disorders (APOE: ε2/ε3/ε4; HFE: H63D; C9ORF72: hexanucleotide expansions ≥ 9 repeats), cognitive/functional impairment (MiniMental State Examination MMSE, Clock Drawing Test CDT, Short Physical Performance Battery SPPB), comorbidities and HIV-related variables in a cohort of > 50 years old PWH (n = 60) with at least 10 years efficient ART. Patients with diabetes or hypertension showed significantly lower MMSE (p = .031) or SPPB (p = .010) scores, respectively, while no relations between HIV-related variables and cognitive/functional scores were observed. Patients with at least one APOEε3 allele had higher CDT scores (p = .019), APOEε2/ε4 patients showing the lowest scores in all tests. Patients with HFE-H63D variant showed more frequently hypertriglyceridemia (p = .023) and those harboring C9ORF72 expansions > 9 repeats had higher CD4-cell counts (p = .032) and CD4% (p = .041). Multiple linear regression analysis computed to verify possible associations among cognitive/functional scores and all variables further suggested positive association between higher CDT scores and the presence of at least one APOEε3 allele (2,2; 95% CI [0,03 0,8]; p = .037), independent of other variables, although the model did not reach the statistical significance (p = .14). These data suggest that in PWH on efficient ART cognitive abilities and physical performances may be partly associated with comorbidities and genetic background. However, further analyses are needed to establish whether they could be also dependent and influenced by comorbidities and genetic background.
衰老导致的认知能力下降受慢性炎症和合并症的影响。在人类免疫缺陷病毒感染患者（HIV 感染者）中，HIV 引起的炎症、生活方式和长期抗逆转录病毒治疗（ART）的影响也可能导致认知障碍。遗传在 HIV 相关神经认知障碍（HAND）的易感性中的作用尚未完全阐明。在这里，我们探讨了参与炎症和神经退行性疾病的 3 个基因（APOE：ε2/ε3/ε4；HFE：H63D；C9ORF72：六核苷酸重复 ≥ 9 次）的变体与认知/功能障碍（简易精神状态检查 MMSE、画钟测验 CDT、简短体能测试 SPPB）、合并症和 HIV 相关变量之间的可能关系，该队列纳入了年龄大于 50 岁且至少接受 10 年高效 ART 的 HIV 感染者（n=60）。患有糖尿病或高血压的患者 MMSE（p=0.031）或 SPPB（p=0.010）评分明显较低，而 HIV 相关变量与认知/功能评分之间未见相关性。至少携带一个 APOEε3 等位基因的患者 CDT 评分更高（p=0.019），而 APOEε2/ε4 患者在所有测试中的得分最低。携带 HFE-H63D 变体的患者更频繁地出现高甘油三酯血症（p=0.023），而携带 C9ORF72 重复次数超过 9 次的患者 CD4 细胞计数（p=0.032）和 CD4%（p=0.041）更高。为了验证认知/功能评分与所有变量之间可能的关联，我们进一步进行了多元线性回归分析，结果表明，在接受高效 ART 的 HIV 感染者中，较高的 CDT 评分与至少携带一个 APOEε3 等位基因之间存在正相关（2,2；95%CI [0,03 0,8]；p=0.037），且独立于其他变量，尽管该模型未达到统计学意义（p=0.14）。这些数据表明，在接受高效 ART 的 HIV 感染者中，认知能力和身体表现可能部分与合并症和遗传背景有关。然而，还需要进一步的分析来确定它们是否也依赖于合并症和遗传背景，并受其影响。
