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APOE ϵ4 and MBL-2 O/O genotypes are associated with neurocognitive impairment in HIV-infected plasma donors

Spector, Stephen Aa; Singh, Kumud Ka; Gupta, Saurabhb; Cysique, Lucette Ad; Jin, Huab; Letendre, Scottc; Schrier, Rachelc; Wu, Zunyoue; Hong, Kun Xe; Yu, Xinf; Shi, Chuanf; Heaton, Robert Kb; the HNRC Group

doi: 10.1097/QAD.0b013e328339e25c
Clinical Science

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 ϵ2, ϵ3 and ϵ4 alleles; MBL2-A/O; CCR5-wt/Δ32; 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/μl 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 ϵ4 allele, 58% were cognitively impaired compared with 31% without the ϵ4 allele (P = 0.001, odds ratio 3.09, 95% confidence interval 1.54–6.18). The mean global deficit score (GDS) for ϵ4-positive participants on antiretrovirals for 12 months was 0.88 (0.55) compared with 0.63 (0.54) for ϵ4-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 ϵ4 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.

aDepartment of Pediatrics, USA

bDepartment of Psychiatry, USA

cDepartment of Medicine, University of California San Diego, La Jolla, California, USA

dUniversity of New South Wales, Sydney, Australia

eNational Center for AIDS/STD Control and Prevention, China

fBeijing Mental Health Institute, Peking University, Beijing, China.

Received 29 December, 2009

Revised 22 February, 2010

Accepted 8 March, 2010

Correspondence to Stephen A. Spector, MD, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0672, USA. Tel: +1 858 534 7055; fax: +1 858 534 7411; e-mail: saspector@ucsd.edu

© 2010 Lippincott Williams & Wilkins, Inc.