Faculty Bibliography
Searched for:
person:bea4
Total Results:
319
MicroRNA associated with atherogenic dyslipidemia in South Asian men [Letter]
PMCID:3809319
PMID: 23871617
ISSN: 1874-1754
CID: 1563672
Epigenetic regulation and measurement of epigenetic changes
Epigenetic mechanisms provide an adaptive layer of control in the regulation of gene expression that enables an organism to adjust to a changing environment. Epigenetic regulation increases the functional complexity of deoxyribonucleic acid (DNA) by altering chromatin structure, nuclear organization, and transcript stability. These changes may additively or synergistically influence gene expression and result in long-term molecular and functional consequences independent of the DNA sequence that may ultimately define an individual's phenotype. This article (1) describes histone modification, DNA methylation, and expression of small noncoding RNA species; (2) reviews the most common methods used to measure these epigenetic changes; and (3) presents factors that need to be considered when choosing a specific tissue to evaluate for epigenetic changes.
PMCID:5839622
PMID: 22661641
ISSN: 1552-4175
CID: 1563682
Host APOL1 genotype is independently associated with proteinuria in HIV infection
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.
PMCID:3788838
PMID: 23715117
ISSN: 1523-1755
CID: 1563692
HIV serostatus differs by catechol-O-methyltransferase Val158Met genotype
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.
PMCID:3897122
PMID: 23807274
ISSN: 1473-5571
CID: 1563702
Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis
BACKGROUND:Non-alcoholic steatohepatitis (NASH) is a common cause of serum alanine aminotransferase (ALT) elevations and chronic liver disease, but it is unclear how well ALT elevations reflect the liver injury. AIM/OBJECTIVE:To assess how well changes in ALT elevations reflect improvements in liver histology in response to vitamin E therapy. METHODS:The vitamin E and placebo arms of the Pioglitazone vs. Vitamin E vs. Placebo in Non-alcoholic Steatohepatitis (PIVENS) trial were reassessed for associations among changes in ALT levels, body weight and liver histology. An ALT response was defined as a decrease to ≤40 U/L and by ≥30% of baseline. Liver biopsies taken before and after treatment were scored for non-alcoholic fatty liver disease activity (NAS) and fibrosis. RESULTS:ALT responses were more frequent among vitamin E (48%) than placebo (16%) recipients (P < 0.001). Among vitamin E recipients, ALT responses were associated with decreases in NAS (P < 0.001), but not fibrosis scores (P = 0.34), whereas among placebo recipients, ALT responses were associated with significant decreases in both (P < 0.05). Weight loss (≥2 kg) was also associated with ALT response (P < 0.001), improvements in NAS (P < 0.001) and fibrosis (P < 0.02), but vitamin E had an added effect both with and without weight loss. Weight gain (≥2 kg) was associated with lack of ALT response and worsening NAS and fibrosis scores in patients not on vitamin E. CONCLUSIONS:Decrease of ALT levels to normal in patients with NASH is usually associated with improved histological activity. Management should stress the value of weight loss and strongly discourage weight gain. Vitamin E can improve both ALT levels and histology with and without weight loss. CLINICAL TRIAL NUMBER/BACKGROUND:NCT00063622.
PMCID:3775262
PMID: 23718573
ISSN: 1365-2036
CID: 5417112
Differences in sleep disturbance, fatigue and energy levels between women with and without breast pain prior to breast cancer surgery
The purpose of this study was to evaluate for differences in occurrence and severity ratings of sleep disturbance, fatigue, and decreased energy in women who reported breast pain prior to surgery for breast cancer. Of the 390 women who completed self-report measures for each symptom, 28.2% reported pain in their breast prior to surgery. A higher percentage of women in the pain group (i.e., 66.7% versus 53.5%) reported clinically meaningful levels of sleep disturbance. However, no between group differences were found in the severity of sleep disturbance, fatigue, or decreased energy. Findings from this study suggest that sleep disturbance, fatigue, and decreased levels of energy are significant problems for women prior to breast cancer surgery. Future studies need to evaluate for specific characteristics that place women at greater risk for these symptoms as well as the mechanisms that underlie these symptoms.
PMCID:3524341
PMID: 22858121
ISSN: 1532-3080
CID: 1563712
Cytokine gene variation is associated with depressive symptom trajectories in oncology patients and family caregivers
PURPOSE: Depressive symptoms are common in cancer patients and their family caregivers (FCs). While these symptoms are characterized by substantial interindividual variability, the factors that predict this variability remain largely unknown. This study sought to confirm latent classes of oncology patients and FCs with distinct depressive symptom trajectories and to examine differences in phenotypic and genotypic characteristics among these classes. METHOD: Among 167 oncology outpatients with breast, prostate, lung, or brain cancer and 85 of their FCs, growth mixture modeling (GMM) was used to identify latent classes of individuals based on Center for Epidemiological Studies-Depression (CES-D) scores obtained prior to, during, and for four months following completion of radiation therapy. One hundred four single nucleotide polymorphisms (SNPs) and haplotypes in 15 candidate cytokine genes were interrogated for differences between the two largest latent classes. Multivariate logistic regression analyses assessed effects of phenotypic and genotypic characteristics on class membership. RESULTS: Four latent classes were confirmed: Resilient (56.3%), Subsyndromal (32.5%), Delayed (5.2%), and Peak (6.0%). Participants who were younger, female, non-white, and who reported higher baseline trait and state anxiety were more likely to be in the Subsyndromal, Delayed, or Peak groups. Variation in three cytokine genes (i.e., interleukin 1 receptor 2 [IL1R2], IL10, tumor necrosis factor alpha [TNFA]), age, and performance status predicted membership in the Resilient versus Subsyndromal classes. CONCLUSIONS: Findings confirm the four latent classes of depressive symptom trajectories previously identified in a sample of breast cancer patients. Variations in cytokine genes may influence variability in depressive symptom trajectories.
PMCID:4114773
PMID: 23187335
ISSN: 1532-2122
CID: 1563722
Journal of acquired immune deficiency syndromes. JAIDS. 2013:63(1):67-76.DOI: 10.1097/QAI.0b013e318289565c
HIV and recent illicit drug use interact to affect verbal memory in women
OBJECTIVE: HIV infection and illicit drug use are each associated with diminished cognitive performance. This study examined the separate and interactive effects of HIV and recent illicit drug use on verbal memory, processing speed, and executive function in the multicenter Women's Interagency HIV Study. METHODS: Participants included 952 HIV-infected and 443 HIV-uninfected women (mean age = 42.8, 64% African-American). Outcome measures included the Hopkins Verbal Learning Test-Revised and the Stroop test. Three drug use groups were compared: recent illicit drug users (cocaine or heroin use in past 6 months, n = 140), former users (lifetime cocaine or heroin use but not in past 6 months, n = 651), and nonusers (no lifetime use of cocaine or heroin, n = 604). RESULTS: The typical pattern of recent drug use was daily or weekly smoking of crack cocaine. HIV infection and recent illicit drug use were each associated with worse verbal learning and memory (P < 0.05). Importantly, there was an interaction between HIV serostatus and recent illicit drug use such that recent illicit drug use (compared with nonuse) negatively impacted verbal learning and memory only in HIV-infected women (P < 0.01). There was no interaction between HIV serostatus and illicit drug use on processing speed or executive function on the Stroop test. CONCLUSIONS: The interaction between HIV serostatus and recent illicit drug use on verbal learning and memory suggests a potential synergistic neurotoxicity that may affect the neural circuitry underlying performance on these tasks.
PMCID:3628722
PMID: 23392462
ISSN: 1944-7884
CID: 1563732
Measurement of MicroRNA: a regulator of gene expression
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.
PMID: 22204760
ISSN: 1552-4175
CID: 1563742
Differences in depression, anxiety, and quality of life between women with and without breast pain prior to breast cancer surgery
PURPOSE OF THE RESEARCH: Little is known about the relationships between pain, anxiety, and depression in women prior to breast cancer surgery. The purpose of this study was to evaluate for differences in anxiety, depression, and quality of life (QOL) in women who did and did not report the occurrence of breast pain prior to breast cancer surgery. We hypothesized that women with pain would report higher levels of anxiety and depression as well as poorer QOL than women without pain. METHODS AND SAMPLE: A total of 390 women completed self-report measures of pain, anxiety depression, and QOL prior to surgery. KEY RESULTS: Women with preoperative breast pain (28%) were significantly younger, had a lower functional status score, were more likely to be Non-white and to have gone through menopause. Over 37% of the sample reported clinically meaningful levels of depressive symptoms. Almost 70% of the sample reported clinically meaningful levels of anxiety. Patients with preoperative breast pain reported significantly higher depression scores and significantly lower physical well-being scores. No between group differences were found for patients' ratings of state and trait anxiety or total QOL scores. CONCLUSIONS: Our a priori hypotheses were only partially supported. Findings from this study suggest that, regardless of pain status, anxiety and depression are common problems in women prior to breast cancer surgery.
PMCID:3524405
PMID: 22892272
ISSN: 1532-2122
CID: 1563752
