title: APOE epsilon4 and MBL-2 O/O genotypes are associated with neurocognitive impairment in HIV-infected plasma donors.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, California 92093-0672, USA. saspector@ucsd.edu
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Spector
authors.forename: Kumud K
authors.initials: KK
authors.lastname: Singh
authors.forename: Saurabh
authors.initials: S
authors.lastname: Gupta
authors.forename: Lucette A
authors.initials: LA
authors.lastname: Cystique
authors.forename: Hua
authors.initials: H
authors.lastname: Jin
authors.forename: Scott
authors.initials: S
authors.lastname: Letendre
authors.forename: Rachel
authors.initials: R
authors.lastname: Schrier
authors.forename: Zunyou
authors.initials: Z
authors.lastname: Wu
authors.forename: Kun X
authors.initials: KX
authors.lastname: Hong
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.forename: Chuan
authors.initials: C
authors.lastname: Shi
authors.forename: Robert K
authors.initials: RK
authors.lastname: Heaton
mesh_terms: D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics*; D001782:Blood Donors; D002681:China; D003072:Cognition Disorders / Q000235:genetics* / Q000503:physiopathology / Q000821:virology; D018450:Disease Progression; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000503:physiopathology / Q000821:virology; D015497:HIV-1; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D009483:Neuropsychological Tests
chemical_list: D001057:Apolipoproteins E; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin