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HIV serostatus differs by catechol-O-methyltransferase Val158Met genotype.

ABSTRACT: The Met allele of the catechol-O-methyltransferase (COMT) Val158Met polymorphism is associated with increased cortical dopamine and risk behaviors including illicit drug use and unprotected sex. Therefore, we examined whether or not the distribution of the Val158Met genotype differed between HIV-infected and HIV-uninfected women.Cross-sectional analysis using data from the Women's Interagency HIV Study (WIHS), the largest longitudinal cohort study of HIV in women.We conducted an Armitage-Cochran test and logistic regression to compare genotype frequencies between 1848 HIV-infected and 612 HIV-uninfected women in WIHS.The likelihood of carrying one or two Met alleles was greater in HIV-infected women (61%) compared to HIV-uninfected women (54%), Z ?=? -3.60, P ?< 0.001.We report the novel finding of an association between the Val158Met genotype and HIV serostatus that may be mediated through the impact of dopamine function on propensity for risk-taking.

SUBMITTER: Sundermann EE

PROVIDER: S-EPMC3897122 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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HIV serostatus differs by catechol-O-methyltransferase Val158Met genotype.

Sundermann Erin E EE Bishop Jeffrey R JR Rubin Leah H LH Aouizerat Bradley B Wilson Tracey E TE Weber Kathleen M KM Cohen Mardge M Golub Elizabeth E Anastos Kathryn K Liu Chenglong C Crystal Howard H Pearce Celeste L CL Maki Pauline M PM

AIDS (London, England) 20130701 11

<h4>Objective</h4>The Met allele of the catechol-O-methyltransferase (COMT) Val158Met polymorphism is associated with increased cortical dopamine and risk behaviors including illicit drug use and unprotected sex. Therefore, we examined whether or not the distribution of the Val158Met genotype differed between HIV-infected and HIV-uninfected women.<h4>Design</h4>Cross-sectional analysis using data from the Women's Interagency HIV Study (WIHS), the largest longitudinal cohort study of HIV in women ...[more]

PMID: 23807274

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Project description:ObjectiveCatechol-O-methyltransferase (COMT), a key enzyme in degrading catecholamines associated with the stress response, may influence susceptibility to delirium. Individuals with the COMT (rs4680) Val/Val genotype (designated "warriors") withstand the onset of neuropsychiatric disorders and cognitive decline, whereas individuals with Met/Met and Val/Met genotypes ("nonwarriors") are more susceptible to these conditions. We evaluated whether COMT genotype modifies the established association between acute phase reactant (stress marker) C-reactive protein (CRP) and postoperative delirium.MethodsThis was a prospective cohort study conducted at two academic medical centers. The study involved 547 patients aged 70 or older undergoing major noncardiac surgery. We collected blood, extracted DNA, and performed COMT genotyping using allele-specific polymerase chain reaction assays, considering warriors versus nonwarriors. High plasma CRP, measured on postoperative day 2 using enzyme-linked immunosorbent assay, was defined by the highest sample-based quartile (≥234.12 mg/L). Delirium was determined using the Confusion Assessment Method, augmented by a validated chart review. We used generalized linear models adjusted for age, sex, surgery type, and race/ethnicity, stratified by COMT genotype, to determine whether the association between CRP and delirium differed by COMT.ResultsPrevalence of COMT warriors was 26%, and postoperative delirium occurred in 23%. Among COMT warriors, high CRP was not associated with delirium (relative risk [RR] 1.0, 95% confidence interval [CI] 0.4-2.6). In contrast, among nonwarriors, we found the expected relationship of high CRP and delirium (RR 1.5, 95% CI 1.1-2.2).ConclusionCOMT warriors may be protected against the increased risk of delirium associated with high CRP on postoperative day 2. With further confirmation, COMT genotype may help target interventions for delirium prevention in the vulnerable nonwarrior group.

Dataset Information

HIV serostatus differs by catechol-O-methyltransferase Val158Met genotype.

Publications

HIV serostatus differs by catechol-O-methyltransferase Val158Met genotype.

Similar Datasets

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