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Publication Abstract Display
Type: Poster
Title: COMT VAL158 MET polymorphism, cardiometabolic risk, and HIV neurocognitive disorder.
Authors: Saloner R, Marquine MJ, Sundermann EE, Hong S, McCutchan J, Ellis RJ, Grant I, Cherner M
Date: 02-20-2019
Abstract:Objective: The Val allele of the Val158Met single-nucleotide poly-morphism of the catechol-o-methyltransferase gene (COMT) codes for 40% more enzymatic activity of COMT than the low activity Met allele, resulting in faster metabolism and reduced bioavailability of dopamine. Among persons living with HIV (PLWH), Val carriers display neurocognitive deficits relative to Met carriers, presumably due to exacerbation of HIV-related depletion of DA. COMT may also regulate cardiometabolic function, which is often dysregulated among PLWH, thus increasing risk for neurocognitive impairment (NCI). We examined whether the effect of cardiometabolic risk on NCI was moderated by COMT and HIV disease severity (i.e., nadir CD4) among PLWH men.Participants and Methods: 329 PLWH men (mean age=44.0) under-went neurocognitive assessment, non-fasting blood draw, and COMTgenotyping. Based on the study sample distributions, Z-scores for BMI, systolic blood pressure, glucose, triglycerides, and HDL cholesterol were averaged to derive a cardiometabolic risk score (CMRS). NCI was defined as demographically-adjusted global deficit score≥0.5. Logistic regression modelled NCI as a function of COMT, CMRS, and their inter-action, covarying for estimated premorbid function, ethnicity, and HIV disease characteristics. Follow-up analysis included a 3-way interaction of COMT, CMRS, and nadir CD4.Results: Genotypes were 81 Met/Met, 147 Val/Met, and 101 Val/Val. Higher CMRS increased risk of NCI among Val/Val (OR=2.13, p<.01), but not Val/Met (OR=0.93, p>.05) or Met/Met (OR=0.92, p>.05). Among Val/Val carriers, the effect of CMRS was moderated by nadir CD4 (p<.01) such that higher CMRS increased the likelihood of NCI only at nadir CD4<180.Conclusions: Results suggest a tripartite model by which genetically-driven low DA reserve, cardiometabolic dysfunction, and historically advanced immunosuppression synergistically enhance risk of NCI, possibly due to neurotoxic inflammation and oxidative stress.

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