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Impact of a 4q25 genetic variant in atrial flutter and on the risk of atrial fibrillation after cavotricuspid isthmus ablation

Roberts, Jason D; Hsu, Jonathan C; Aouizerat, Bradley E; Pullinger, Clive R; Malloy, Mary J; Kane, John P; Olgin, Jeffrey E; Marcus, Gregory M
BACKGROUND: The prediction of atrial fibrillation (AF) following catheter ablation of atrial flutter (Afl) would be helpful to facilitate targeted arrhythmia monitoring and anti-coagulation strategies. A single nucleotide polymorphism, rs2200733, is strongly associated with AF. We sought to characterize the association between rs2200733 and prevalent Afl and to determine if the variant could predict AF after cavotricuspid isthmus ablation. METHODS AND RESULTS: We performed a genetic association study of 295 patients with Afl and/or AF and 469 controls using multivariable logistic regression. The variant was then assessed as a predictor of incident AF after cavotricuspid isthmus ablation in 87 consecutive typical Afl patients with Cox proportional hazards models. The rs2200733 rare allele was associated with an adjusted 2.06-fold increased odds of isolated Afl (95% CI: 1.13-3.76, P = 0.019) and an adjusted 2.79-fold increased odds of a combined phenotype of AF and Afl (95% CI: 1.81-4.28, P < 0.001). Following catheter ablation for Afl, carrier status of rs2200733 failed to predict an increased risk of AF either among all subjects (adjusted HR: 0.94; 95% CI: 0.58-1.53, P = 0.806) or among those with isolated Afl (adjusted HR: 1.29; 95% CI: 0.51-3.26, P = 0.585). CONCLUSIONS: Our study demonstrates that Afl, whether occurring in isolation or along with AF, is associated with the rs2200733 AF risk allele. Genetic carrier status of rs2200733 failed to predict an increased risk of incident or recurrent AF following catheter ablation for Afl. These findings suggest that the causal mechanism associated with rs2200733 is germane to both AF and Afl.
PMCID:3947706
PMID: 24237655
ISSN: 1540-8167
CID: 1563592

Associations Between Cytokine Gene Variations and Severe Persistent Breast Pain in Women Following Breast Cancer Surgery

Stephens, Kimberly; Cooper, Bruce A; West, Claudia; Paul, Steven M; Baggott, Christina R; Merriman, John D; Dhruva, Anand; Kober, Kord M; Langford, Dale J; Leutwyler, Heather; Luce, Judith A; Schmidt, Brian L; Abrams, Gary M; Elboim, Charles; Hamolsky, Deborah; Levine, Jon D; Miaskowski, Christine; Aouizerat, Bradley E
Persistent pain following breast cancer surgery is a significant clinical problem. Although immune mechanisms may play a role in the development and maintenance of persistent pain, few studies have evaluated for associations between persistent breast pain following breast cancer surgery and variations in cytokine genes. In this study, associations between previously identified extreme persistent breast pain phenotypes (ie, no pain vs severe pain) and single nucleotide polymorphisms (SNPs) spanning 15 cytokine genes were evaluated. In unadjusted analyses, the frequency of 13 SNPs and 3 haplotypes in 7 genes differed significantly between the no pain and severe pain classes. After adjustment for preoperative breast pain and the severity of average postoperative pain, 1 SNP (ie, interleukin [IL] 1 receptor 2 rs11674595) and 1 haplotype (ie, IL10 haplotype A8) were associated with pain group membership. These findings suggest a role for cytokine gene polymorphisms in the development of persistent breast pain following breast cancer surgery. PERSPECTIVE: This study evaluated for associations between cytokine gene variations and the severity of persistent breast pain in women following breast cancer surgery. Variations in 2 cytokine genes were associated with severe breast pain. The results suggest that cytokines play a role in the development of persistent postsurgical pain.
PMCID:4331184
PMID: 24411993
ISSN: 1526-5900
CID: 741422

Association between an interleukin 1 receptor, type I promoter polymorphism and self-reported attentional function in women with breast cancer

Merriman, John D; Aouizerat, Bradley E; Cataldo, Janine K; Dunn, Laura; Cooper, Bruce A; West, Claudia; Paul, Steven M; Baggott, Christina R; Dhruva, Anand; Kober, Kord; Langford, Dale J; Leutwyler, Heather; Ritchie, Christine S; Abrams, Gary; Dodd, Marylin; Elboim, Charles; Hamolsky, Deborah; Melisko, Michelle; Miaskowski, Christine
Subgroups of patients with breast cancer may be at greater risk for cytokine-induced changes in cognitive function after diagnosis and during treatment. The purposes of this study were to identify subgroups of patients with distinct trajectories of attentional function and evaluate for phenotypic and genotypic (i.e., cytokine gene polymorphisms) predictors of subgroup membership. Self-reported attentional function was evaluated in 397 patients with breast cancer using the Attentional Function Index before surgery and for six months after surgery (i.e., seven time points). Using growth mixture modeling, three attentional function latent classes were identified: High (41.6%), Moderate (25.4%), and Low-moderate (33.0%). Patients in the Low-moderate class were significantly younger than those in the High class, with more comorbidities and lower functional status than the other two classes. No differences were found among the classes in years of education, race/ethnicity, or other clinical characteristics. DNA was recovered from 302 patients' samples. Eighty-two single nucleotide polymorphisms among 15 candidate genes were included in the genetic association analyses. After controlling for age, comorbidities, functional status, and population stratification due to race/ethnicity, IL1R1 rs949963 remained a significant genotypic predictor of class membership in the multivariable model. Carrying the rare "A" allele (i.e., GA+AA) was associated with a twofold increase in the odds of belonging to a lower attentional function class (OR: 1.98; 95% CI: 1.18, 3.30; p=.009). Findings provide evidence of subgroups of women with breast cancer who report distinct trajectories of attentional function and of a genetic association between subgroup membership and an IL1R1 promoter polymorphism.
PMCID:3927406
PMID: 24315345
ISSN: 1096-0023
CID: 1563612

Associations between cytokine gene variations and self-reported sleep disturbance in women following breast cancer surgery

Alfaro, Emely; Dhruva, Anand; Langford, Dale J; Koetters, Theresa; Merriman, John D; West, Claudia; Dunn, Laura B; Paul, Steven M; Cooper, Bruce; Cataldo, Janine; Hamolsky, Deborah; Elboim, Charles; Kober, Kord; Aouizerat, Bradley E; Miaskowski, Christine
PURPOSE OF THE RESEARCH: To attempt to replicate the associations found in our previous study of patients and family caregivers between interleukin 6 (IL6) and nuclear factor kappa beta 2 (NFKB2) and sleep disturbance and to identify additional genetic associations in a larger sample of patients with breast cancer. METHODS AND SAMPLE: Patients with breast cancer (n = 398) were recruited prior to surgery and followed for six months. Patients completed a self-report measure of sleep disturbance and provided a blood sample for genomic analyses. Growth mixture modeling was used to identify distinct latent classes of patients with higher and lower levels of sleep disturbance. KEY RESULTS: Patients who were younger and who had higher comorbidity and lower functional status were more likely to be in the high sustained sleep disturbance class. Variations in three cytokine genes (i.e., IL1 receptor 2 (IL1R2), IL13, NFKB2) predicted latent class membership. CONCLUSIONS: Polymorphisms in cytokine genes may partially explain inter-individual variability in sleep disturbance. Determination of high risk phenotypes and associated molecular markers may allow for earlier identification of patients at higher risk for developing sleep disturbance and lead to the development of more targeted clinical interventions.
PMCID:3946647
PMID: 24012192
ISSN: 1532-2122
CID: 1563622

Telomere length is associated with sleep duration but not sleep quality in adults with human immunodeficiency virus

Lee, Kathryn A; Gay, Caryl; Humphreys, Janice; Portillo, Carmen J; Pullinger, Clive R; Aouizerat, Bradley E
BACKGROUND AND STUDY OBJECTIVE: Telomere length provides an estimate of cellular aging and is influenced by oxidative stress and health behaviors such as diet and exercise. This article describes relationships between telomere length and sleep parameters that included total sleep time (TST), wake after sleep onset (WASO), and self-reported sleep quality in a sample of adults with chronic illness. DESIGN AND PARTICIPANTS: Cross-sectional study of 283 adults (74% male, 42% Caucasian) infected with human immunodeficiency virus (HIV) while living in the San Francisco Bay area, CA, USA. Ages ranged from 22-77 y. MEASUREMENTS AND RESULTS: TST and WASO were estimated with wrist actigraphy across 72 h; self-reported sleep quality was assessed with the Pittsburgh Sleep Quality Index. Relative telomere length (RTL) in leukocytes was estimated by quantitative polymerase chain reaction assays. Shorter RTL was associated with older age, and RTL was shorter in males than females. RTL was unrelated to HIV disease characteristics. RTL was not associated with WASO or self-reported sleep quality. Participants with at least 7 h sleep had longer RTL than those with less than 7 h, even after controlling for the effects of age, sex, race, education, body mass index, metabolic hormones (i.e., leptin, ghrelin, adiponectin, and resistin), depression and anxiety, and sleep quality. CONCLUSION: Results suggest that sleep duration is associated with preserving telomere length in a population of human immunodeficiency virus-infected adults. Getting at least 7 hours of sleep at night may either protect telomeres from damage or restore them on a nightly basis.
PMCID:3902878
PMID: 24470704
ISSN: 1550-9109
CID: 1563632

Contribution of sleep disturbance to cancer fatigue

Chapter by: Miaskowski, Christine; Aouizerat, Bradley E.
in: Impact of Sleep and Sleep Disturbances on Obesity and Cancer by
[S.l.] : Springer New York, 2014
pp. 169-192
ISBN: 9781461495260
CID: 2803922

Longitudinal assessment of high blood pressure in children with nonalcoholic fatty liver disease

Schwimmer, Jeffrey B; Zepeda, Anne; Newton, Kimberly P; Xanthakos, Stavra A; Behling, Cynthia; Hallinan, Erin K; Donithan, Michele; Tonascia, James; Abrams, Stephanie H; Barlow, Sarah; Himes, Ryan; Krisnamurthy, Rajesh; Maldonado, Leanel; Morris, Beverly; Bernstein, Kimberlee; Cecil, Kim; DeVore, Stephanie; Kohli, Rohit; Lake, Kathleen; Podberesky, Daniel; Slaughter, Crystal; Xanthakos, Stavra; Behr, Gerald; Lavine, Joel E; Mencin, Ali; Ovchinsky, Nadia; Reynoso, Elena; Alazraki, Adina; Cleeton, Rebecca; Karpen, Saul; Raviele, Nicholas; Vos, Miriam; Byam, Elizabeth; Cummings, Oscar W; Fleming, Cynthia; Klipsch, Ann; Molleston, Jean P; Sandrasegaran, Kumar; Subbarao, Girish; Pfeifer, Kimberly; Scheimann, Ann; Torbenson, Michael; Arnon, Ronen; Boyd, Mariel; Amsden, Katie; Fishbein, Mark H; Kirwan, Elizabeth; Mohammad, Saeed; Quinn, Ann; Rigsby, Cynthia; Whitington, Peter F; Derdoy, Jose; Jain, Ajay; King, Debra; Osmack, Pat; Siegner, Joan; Stewart, Susan; Romo, Dana; Angeles, Jorge; Arroyo, Sandra; Awai, Hannah I; Behling, Cynthia; Bross, Craig; Collins, Jennifer; Durelle, Janis; Middleton, Michael; Newton, Kimberly; Paiz, Melissa; Schwimmer, Jeffrey B; Sirlin, Claude; Ugalde-Nicalo, Patricia; Zepeda, Anne; Aouizerat, Bradley; Ferrell, Linda D; Fleck, Shannon; Gill, Ryan; Langlois, Camille; Perito, Emily Rothbaum; Rosenthal, Philip; Tsai, Patrika; Cooper, Kara; Horslen, Simon; Hsu, Evelyn; Murray, Karen; Otto, Randolph; Rich, Deana; Yeh, Matthew; Young, Melissa; Brunt, Elizabeth M; Fowler, Kathryn; Kleiner, David E; Grave, Gilman D; Doo, Edward C; Hoofnagle, Jay H; Robuck, Patricia R; Sherker, Averell; Belt, Patricia; Clark, Jeanne M; Hallinan, Erin; Donithan, Michele; Isaacson, Milana; May, Kevin P; Miriel, Laura; Sternberg, Alice; Tonascia, James; Ünalp-Arida, Aynur; Van Natta, Mark; Vaughn, Ivana; Wilson, Laura; Yates, Katherine
OBJECTIVE:Nonalcoholic fatty liver disease (NAFLD) affects 9.6% of children and may put these children at elevated risk of high blood pressure and subsequent cardiovascular morbidity and mortality. Therefore, we sought to determine the prevalence of and risk factors for high blood pressure in children with NAFLD. METHODS:Cohort study performed by the NIDDK NASH Clinical Research Network. There were 484 children with NAFLD ages 2 to 17 at enrollment; 382 children were assessed both at enrollment and 48 weeks afterwards. The main outcomes were high blood pressure at baseline and persistent high blood pressure at both baseline and 48 weeks. RESULTS:Prevalence of high blood pressure at baseline was 35.8% and prevalence of persistent high blood pressure was 21.4%. Children with high blood pressure were significantly more likely to have worse steatosis than children without high blood pressure (mild 19.8% vs. 34.2%, moderate 35.0% vs. 30.7%, severe 45.2% vs. 35.1%; P = 0.003). Higher body mass index, low-density lipoprotein, and uric acid were independent risk factors for high blood pressure (Odds Ratios: 1.10 per kg/m2, 1.09 per 10 mg/dL, 1.25 per mg/dL, respectively). Compared to boys, girls with NAFLD were significantly more likely to have persistent high blood pressure (28.4% vs.18.9%; P = 0.05). CONCLUSIONS:In conclusion, NAFLD is a common clinical problem that places children at substantial risk for high blood pressure, which may often go undiagnosed. Thus blood pressure evaluation, control, and monitoring should be an integral component of the clinical management of children with NAFLD.
PMCID:4242611
PMID: 25419656
ISSN: 1932-6203
CID: 5417122

MicroRNA associated with dyslipidemia and coronary disease in humans

Flowers, Elena; Aouizerat, Bradley E
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 gene-environment interactions.
PMCID:3882685
PMID: 24170031
ISSN: 1531-2267
CID: 1563642

Differences in morning and evening fatigue in oncology patients and their family caregivers

Dhruva, Anand; Aouizerat, Bradley E; Cooper, Bruce; Paul, Steven M; Dodd, Marylin; West, Claudia; Wara, William; Lee, Kathryn; Dunn, Laura B; Langford, Dale J; Merriman, John D; Baggott, Christina; Cataldo, Janine; Ritchie, Christine; Kober, Kord; Leutwyler, Heather; Miaskowski, Christine
PURPOSE OF THE RESEARCH: To identify distinct latent classes of individuals based on ratings of morning and evening fatigue; evaluate for differences in phenotypic characteristics, as well as symptom and quality of life scores, among these latent classes; and evaluate for an overlap in morning and evening fatigue class membership. PATIENTS AND METHODS: In a sample of 167 oncology outpatients and 85 of their FCs, growth mixture modeling was used to identify distinct latent classes based on ratings of morning and evening fatigue obtained before, during, and after radiation therapy. Analyses of variance and Chi Square analyses were used to evaluate for differences among the morning and evening fatigue latent classes. RESULTS: Three distinct latent classes for morning fatigue were identified. Participants in the High Morning Fatigue class (47%) were younger and had lower functional status. Three distinct latent classes for evening fatigue were identified. Participants in the High Evening Fatigue class (61%) were younger, more likely to be female, more likely to have children at home, and more likely to be a FC. Only 10.3% of participants were classified in both the Very Low Morning and Low Evening Fatigue classes and 41.3% were classified in both the High Morning and High Evening Fatigue classes. CONCLUSIONS: Different characteristics were associated with morning and evening fatigue, which suggests that morning and evening fatigue may be distinct but related symptoms. Additional research is needed to elucidate the mechanisms that may underlie diurnal variability in fatigue.
PMCID:3867806
PMID: 24012189
ISSN: 1532-2122
CID: 1563652

Proposed mechanisms for cancer- and treatment-related cognitive changes

Merriman, John D; Von Ah, Diane; Miaskowski, Christine; Aouizerat, Bradley E
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.
PMCID:3817493
PMID: 24183157
ISSN: 1878-3449
CID: 1563662