Bradley E. Aouizerat

Abstract

OBJECTIVE: 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. DESIGN: Cross-sectional analysis using data from the Women's Interagency HIV Study (WIHS), the largest longitudinal cohort study of HIV in women. METHODS: We conducted an Armitage-Cochran test and logistic regression to compare genotype frequencies between 1848 HIV-infected and 612 HIV-uninfected women in WIHS. RESULTS: 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. CONCLUSION: 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.

Abstract

Proteinuria is associated with adverse clinical outcomes in HIV infection. Here we evaluated whether APOL1 risk alleles, previously associated with advanced kidney disease, are independently associated with proteinuria in HIV infection in a cross-sectional study of HIV-infected women in the Women's Interagency HIV Study. We estimated the percent difference in urine protein excretion and odds of proteinuria (≥200 mg/g) associated with two versus one or no APOL1 risk allele using linear and logistic regression, respectively. Of 1285 women successfully genotyped, 379 carried one and 80 carried two risk alleles. Proteinuria was present in 124 women, 78 of whom had proteinuria confirmed on a second sample. In women without prior AIDS, two risk alleles were independently associated with a 69% higher urine protein excretion (95% confidence interval (CI): 36, 108) and five-fold higher odds of proteinuria (95% CI: 2.45, 10.37) as compared with one or no risk allele. No association was found in women with prior AIDS. Analyses in which women with impaired kidney function were excluded and proteinuria was confirmed by a second urine sample yielded similar estimates. Thus, APOL1 risk alleles are associated with significant proteinuria in HIV-infected persons without prior clinical AIDS, independent of clinical factors traditionally associated with proteinuria. Trials are needed to determine whether APOL1 genotyping identifies individuals who could benefit from earlier intervention to prevent overt renal disease.

Abstract

Context: Fatigue is a prevalent symptom among adults living with HIV. There is increasing evidence that fatigue and energy are related, yet distinct constructs. Although HIV-related fatigue has been well studied, little is known about perceived energy and how it relates to fatigue, individual characteristics, and other symptoms. Objectives: To describe the experience of perceived energy in adults with HIV and evaluate its relationship to demographic and clinical characteristics as well as symptoms of fatigue, sleep disturbance, anxiety, depression, and daytime function. Methods: The design was descriptive, comparative, and correlational. The sample of 318 adults with HIV completed a demographic questionnaire; the Memorial Symptom Assessment Scale; and measures of fatigue, sleep disturbance, anxiety, depressive symptoms, and daytime function. Medical records were reviewed for disease and treatment data. Participants who reported a lack of energy were compared with those who did not on demographic, clinical, and symptom variables. Regression models of perceived energy and its interference with daytime function also were evaluated. Results: Perceived lack of energy was highly prevalent (65%) and more strongly related to interference with daytime function than more general measures of fatigue severity, even when controlling for other characteristics and symptoms. Like other aspects of fatigue, lack of energy was associated with sleep disturbance, anxiety, and depressive symptoms. Lack of energy was more strongly related to morning fatigue than to evening fatigue. Conclusion: Lack of energy interferes with daytime function and is not just the inverse of fatigue but a distinct perception that differs from fatigue.

Abstract

The purposes of this study were to evaluate for differences in phenotypic and genotypic characteristics in women who did and did not develop lymphedema (LE) following breast cancer treatment. Breast cancer patients completed a number of self-report questionnaires. LE was evaluated using bioimpedance spectroscopy. Genotyping was done using a custom genotyping array. No differences were found between patients with (n = 155) and without LE (n = 387) for the majority of the demographic and clinical characteristics. Patients with LE had a significantly higher body mass index, more advanced disease and a higher number of lymph nodes removed. Genetic associations were identified for four genes (i.e., lymphocyte cytosolic protein 2 (rs315721), neuropilin-2 (rs849530), protein tyrosine kinase (rs158689), vascular cell adhesion molecule 1 (rs3176861)) and three haplotypes (i.e., Forkhead box protein C2 (haplotype A03), neuropilin-2 (haplotype F03), vascular endothelial growth factor-C (haplotype B03)) involved in lymphangiogensis and angiogenesis. These genetic associations suggest a role for a number of lymphatic and angiogenic genes in the development of LE following breast cancer treatment.

Abstract

MicroRNAs (miRs) are epigenetic regulators of messenger RNAs' (mRNA) expression of polypeptides. As such, miRs represent an intriguing mechanism by which gene-environment interactions are hypothesized to occur on the level of epigenetic control over gene expression. In addition to promising findings from in vitro studies indicating that miRs have the potential to function as therapeutic agents in modifying the course of pathophysiologic conditions, recent human studies revealed changes in miR expression patterns in response to behavioral interventions. The authors provide an overview of how miRs are preserved and isolated from other genetic material and describe commonly used methods for measuring miR in the research setting, including Northern blot, polymerase chain reaction, and microarray. The authors also introduce bioinformatic approaches to analysis of high-throughput miR expression and techniques used to create predictive models of miR-mRNA binding to describe possible physiologic pathways affected by specific miRs.

Abstract

MicroRNAs are structural components of an epigenetic mechanism of posttranscriptional regulation of messenger RNA translation. Recently, there has been significant interest in the application of microRNA as a blood-based biomarker of underlying physiological conditions. Dyslipidemia is a complex, heterogeneous condition conferring substantially increased risk for cardiovascular disease. The purpose of this review is to describe the current body of knowledge on the role of microRNA regulation of lipoprotein metabolism in humans and to discuss relevant methodological and study design considerations. We highlight the potential roles for microRNA in geneenvironment interactions.

Abstract

MicroRNAs are structural components of an epigenetic mechanism of post-transcriptional regulation of messenger RNA translation. Recently, there is significant interest in the application of microRNA as a blood-based biomarker of underlying physiologic conditions, and the therapeutic administration of microRNA inhibitors and mimics. The purpose of this review is to describe the current body of knowledge on microRNA regulation of genes involved in lipid metabolism, and to introduce the role of microRNA in development and progression of atherosclerosis.

Abstract

Objectives: To review the proposed mechanisms of cognitive changes associated with non-central nervous system cancers and cancer treatment. Data Sources: Review and synthesis of databased publications and review articles. Conclusion: Proposed mechanisms include cytokine upregulation, hormonal changes, neurotransmitter dysregulation, attentional fatigue, genetic predisposition, and comorbid symptoms. Implications for Nursing Practice: Oncology nurses need to understand the multiple mechanisms that may contribute to the development of cancer- and treatment-related cognitive changes so that they can identify patients at high risk and help patients understand why these changes occur.

Abstract

Context: Sleep disturbance is a problem for oncology patients. Objectives: To evaluate how sleep disturbance and daytime sleepiness (DS) changed from before to six months following surgery and whether certain characteristics predicted initial levels and/or the trajectories of these parameters. Methods: Patients (n = 396) were enrolled prior to surgery and completed monthly assessments for six months following surgery. The General Sleep Disturbance Scale was used to assess sleep disturbance and DS. Using hierarchical linear modeling, demographic, clinical, symptom, and psychosocial adjustment characteristics were evaluated as predictors of initial levels and trajectories of sleep disturbance and DS. Results: All seven General Sleep Disturbance Scale scores were above the cutoff for clinically meaningful levels of sleep disturbance. Lower performance status; higher comorbidity, attentional fatigue, and physical fatigue; and more severe hot flashes predicted higher preoperative levels of sleep disturbance. Higher levels of education predicted higher sleep disturbance scores over time. Higher levels of depressive symptoms predicted higher preoperative levels of sleep disturbance, which declined over time. Lower performance status; higher body mass index; higher fear of future diagnostic tests; not having had sentinel lymph node biopsy; having had an axillary lymph node dissection; and higher depression, physical fatigue, and attentional fatigue predicted higher DS prior to surgery. Higher levels of education, not working for pay, and not having undergone neo-adjuvant chemotherapy predicted higher DS scores over time. Conclusion: Sleep disturbance is a persistent problem for patients with breast cancer. The effects of interventions that can address modifiable risk factors need to be evaluated.