载脂蛋白 E ɛ4 和甘露糖结合凝集素-2 O/O 基因型与 HIV 感染的血浆供者的神经认知障碍相关。
APOE epsilon4 and MBL-2 O/O genotypes are associated with neurocognitive impairment in HIV-infected plasma donors.
机构信息
Department of Pediatrics, University of California San Diego, La Jolla, California 92093-0672, USA.
出版信息
AIDS. 2010 Jun 19;24(10):1471-9. doi: 10.1097/QAD.0b013e328339e25c.
BACKGROUND
Host genetic factors are important determinants for risk of HIV-1 infection and disease progression. This study examined associations of host genetic variants and neurocognitive impairment in Chinese individuals infected through contaminated blood products.
METHODS
Two hundred and one HIV-infected patients from Anhui, China, had neuropsychological tests at baseline and 12 months. DNA was genotyped for APOE epsilon2, epsilon3 and epsilon4 alleles; MBL2-A/O; CCR5-wt/Delta32; CCR5-59029-G/A; CCR2-180-G/A; SDF-1-G/A; IL4-589-C/T; MCP-1-2518-A/G; CX3CR1-745-G/A; -849-C/T polymorphisms and CCL3L1 copy number variants using real-time PCR. Univariate and multivariate analyses were performed.
RESULTS
The cohort included 61% men, with mean education 5.5 years, AIDS diagnosis 113 (55%), on antiretrovirals 114 (56%), mean baseline CD4(+) cell count 349 cells/microl and mean log10 RNA 4.09. At baseline, 37% had global neuropsychological impairment increasing to 44% after 12 months. Of 43 patients with the APOE epsilon4 allele, 58% were cognitively impaired compared with 31% without the epsilon4 allele (P = 0.001, odds ratio 3.09, 95% confidence interval 1.54-6.18). The mean global deficit score (GDS) for epsilon4-positive participants on antiretrovirals for 12 months was 0.88 (0.55) compared with 0.63 (0.54) for epsilon4-negative participants (P = 0.053, 95% confidence interval -0.004 to 0.51). For MBL2, 52% of patients with the O/O genotype declined in cognitive function over 12 months compared with 23% with A/A (odds ratio 3.62, 95% confidence interval 1.46-9.03, P = 0.004). No associations were observed for the other genetic variants.
CONCLUSION
The APOE epsilon4 allele was associated with increased risk for cognitive deficits, whereas the MBL2 O/O genotype was associated with increased risk for progressive cognitive decline in Chinese individuals infected with HIV through contaminated blood products.
背景
宿主遗传因素是影响 HIV-1 感染和疾病进展风险的重要决定因素。本研究旨在探讨中国经血液污染制品感染的个体中宿主遗传变异与神经认知障碍的相关性。
方法
201 名来自中国安徽的 HIV 感染者在基线和 12 个月时进行神经心理学测试。采用实时 PCR 法对 APOE epsilon2、epsilon3 和 epsilon4 等位基因、MBL2-A/O、CCR5-wt/Delta32、CCR5-59029-G/A、CCR2-180-G/A、SDF-1-G/A、IL4-589-C/T、MCP-1-2518-A/G、CX3CR1-745-G/A、-849-C/T 多态性和 CCL3L1 拷贝数变异进行基因分型。采用单变量和多变量分析。
结果
该队列包括 61%的男性，平均受教育年限为 5.5 年，艾滋病诊断为 113 例（55%），接受抗逆转录病毒治疗的有 114 例（56%），平均基线 CD4+细胞计数为 349 个/μl，平均 log10 RNA 为 4.09。基线时有 37%的患者存在全脑认知障碍，12 个月后增加至 44%。在 43 名携带 APOE epsilon4 等位基因的患者中，58%存在认知障碍，而不携带 epsilon4 等位基因的患者为 31%（P=0.001，优势比 3.09，95%置信区间 1.54-6.18）。在接受抗逆转录病毒治疗 12 个月的 epsilon4 阳性参与者中，全球缺陷评分（GDS）的平均值为 0.88（0.55），而 epsilon4 阴性参与者的 GDS 平均值为 0.63（0.54）（P=0.053，95%置信区间 -0.004 至 0.51）。MBL2 方面，O/O 基因型的患者中有 52%在 12 个月内认知功能下降，而 A/A 基因型的患者为 23%（优势比 3.62，95%置信区间 1.46-9.03，P=0.004）。未观察到其他遗传变异与认知障碍之间存在相关性。
结论
APOE epsilon4 等位基因与认知缺陷风险增加相关，而 MBL2 O/O 基因型与中国经血液污染制品感染 HIV 的个体认知功能进行性下降风险增加相关。
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