Iron-regulatory genes are associated with Neuroimaging measures in HIV infection

AbstractThe pathogenesis of HIV-associated neurocognitive impairment (NCI) may involve iron dysregulation. In 243 HIV-seropositive adults without severe comorbidities, we therefore genotyped 250 variants in 20 iron-related genes and evaluated their associations with magnetic resonance imaging measures of brain structure and metabolites, including measures previously linked to NCI. Multivariable regression analyses examined associations between genetic variants and neuroimaging measures, adjusting for relevant covariates and multiple testing. Exploratory analyses stratified by NCI (Global Deficit Score  ≥ 0.5 vs.<0.5), virus detectability in plasma, and comorbidity levels were also performed. Of 27 variants (in 12 iron-regulatory genes) associated with neuroimaging measures after correction for the 37 haplotype blocks represented, 3 variants survived additional correction for the 21 neuroimaging measures evaluated and demonstrated biologically plausible associations.SLC11A1 rs7576974_T was significantly associated with higher frontal gray matterN-acetylaspartate (p = 3.62e−5). Among individuals with detectable plasma virus,TFRC rs17091382_A was associated with smaller subcortical gray matter volume (p = 3.23e−5), andCP rs4974389_A (p = 3.52e−5) was associated with higher basal ganglia Choline in persons with mild comorbidities. Two other strong associations were observed for variants inSLC40A1 andACO2 but were not robust due to low minor-allele frequ...

Source: Brain Imaging and Behavior - July 2, 2019 Category: Neurology Source Type: research