Elena Flowers

MicroRNA regulation of lipid metabolism

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.

MicroRNAs associated with exercise and diet: a systematic review

MicroRNAs are posttranscriptional regulators of gene expression. MicroRNAs reflect individual biologic adaptation to exposures in the environment. As such, measurement of circulating microRNAs presents an opportunity to evaluate biologic changes associated with behavioral interventions (i.e., exercise, diet) for weight loss. The aim of this study was to perform a systematic review of the literature to summarize what is known about circulating microRNAs associated with exercise, diet, and weight loss. We performed a systematic review of three scientific databases. We included studies reporting on circulating microRNAs associated with exercise, diet, and weight loss in humans. Of 1,219 studies identified in our comprehensive database search, 14 were selected for inclusion. Twelve reported on microRNAs associated with exercise, and two reported on microRNAs associated with diet and weight loss. The majority of studies used a quasiexperimental, cross-sectional design. There were numerous differences in the type and intensity of exercise and dietary interventions, the biologic source of microRNAs, and the methodological approaches used quantitate microRNAs. Data from several studies support an association between circulating microRNAs and exercise. The evidence for an association between circulating microRNAs and diet is weaker because of a small number of studies. Additional research is needed to validate previous observations using methodologically rigorous approaches to microRNA quantitation to determine the specific circulating microRNA signatures associated with behavioral approaches to weight loss. Future directions include longitudinal studies to determine if circulating microRNAs are predictive of response to behavioral interventions.

Prevalence of Metabolic Syndrome in South Asians Residing in the United States

AIMS/HYPOTHESIS The aim of this study was to define the prevalence of the metabolic syndrome and its component risk factors among individuals of South Asian origin living in the United States. METHODS We analyzed baseline data from 1,445 participants enrolled in a cohort study investigating risk factors for cardiovascular disease in South Asians. We defined the metabolic syndrome using the International Diabetes Federation criteria for waist circumference (>90 cm for men; >80 cm, women), triglycerides (>150 mg/dL), high-density lipoprotein cholesterol (HDL-C) (<40 mg/dL (men), < mg/dL (women)), blood pressure (>135/80 mmHg), and fasting glucose (>100 mg/dL). RESULTS The mean age was 43 +/-10 years, and 30% of participants were women. The prevalence of metabolic syndrome was 27% (31% men vs. 17% women, P < 0.05). Fifty-nine percent of the cohort had high waist circumference (58% men vs. 62% women, P = not significant [N.S.]), 47% had low HDL-C [46% men vs. 48% women (NS)], 19% had elevated triglycerides (23% men vs. 8% women, P < 0.05), 14% had hypertension (16% men vs. 9% women, P < 0.05), and 13% had elevated fasting glucose (18% men vs. 11% women, P < 0.05). The most common metabolic syndrome phenotype is low HDL-C with elevated triglycerides. CONCLUSIONS Although the prevalence of the metabolic syndrome is lower than previous reports of South Asians, the prevalence is still unacceptably high despite the presence of protective demographic factors.

Circulating microRNA-320a and microRNA-486 predict thiazolidinedione response: Moving towards precision health for diabetes prevention

INTRODUCTION The aims of this study were to compare microRNA (miR) expression between individuals with and without insulin resistance and to determine whether miRs predict response to thiazolidinedione treatment. MATERIALS AND METHODS In a sample of 93 healthy adults, insulin resistance was defined as steady state plasma glucose (SSPG)≥180 mg/dL and insulin sensitive as <120 mg/dL. Response to thiazolidinedione therapy was defined as ≥10% decrease in SSPG. We selected a panel of microRNAs based on prior evidence for a role in insulin or glucose metabolism. Fold change and Wilcoxon rank sum tests were calculated for the 25 miRs measured. RESULTS At baseline, 81% (n=75) of participants were insulin resistant. Five miRs were differentially expressed between the insulin resistant and sensitive groups: miR-193b (1.45 fold change (FC)), miR-22-3p (1.15 FC), miR-320a (1.36 FC), miR-375 (0.59 FC), and miR-486 (1.21 FC) (all p<0.05). In the subset who were insulin resistant at baseline and received thiazolidinediones (n=47), 77% (n=36) showed improved insulin sensitivity. Six miRs were differentially expressed between responders compared to non-responders: miR-20b-5p (1.20 FC), miR-21-5p, (0.92 FC), miR-214-3p (1.13 FC), miR-22-3p (1.14 FC), miR-320a (0.98 FC), and miR-486-5p (1.25 FC) (all p<0.05). DISCUSSION This study is the first to report miRs associated with response to a pharmacologic intervention for insulin resistance. MiR-320a and miR-486-5p identified responders to thiazolidinedione therapy among the insulin resistant group.

Gene-environment interactions in cardiovascular disease

Background: Historically, models to describe disease were exclusively nature-based or nurture-based. Current theoretical models for complex conditions such as cardiovascular disease acknowledge the importance of both biologic and non-biologic contributors to disease. A critical feature is the occurrence of interactions between numerous risk factors for disease. The interaction between genetic (i.e. biologic, nature) and environmental (i.e. non-biologic, nurture) causes of disease is an important mechanism for understanding both the etiology and public health impact of cardiovascular disease. Objectives: The purpose of this paper is to describe theoretical underpinnings of gene–environment interactions, models of interaction, methods for studying gene–environment interactions, and the related concept of interactions between epigenetic mechanisms and the environment. Discussion: Advances in methods for measurement of genetic predictors of disease have enabled an increasingly comprehensive understanding of the causes of disease. In order to fully describe the effects of genetic predictors of disease, it is necessary to place genetic predictors within the context of known environmental risk factors. The additive or multiplicative effect of the interaction between genetic and environmental risk factors is often greater than the contribution of either risk factor alone.

MicroRNA associated with atherogenic dyslipidemia in South Asian men.

BACKGROUND MicroRNA are an epigenetic post-transcriptional regulatory mechanism of messenger RNA translation, and are potential biomarkers of pathophysiology and response to interventions. MicroRNA...

Use of plasma triglyceride/high-density lipoprotein cholesterol ratio to identify increased cardio-metabolic risk in young, healthy South Asians

Background & objectives: Prevalence of insulin resistance and associated dyslipidaemia [high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentrations] are increased in South Asian individuals; likely contributing to their increased risk of type-2 diabetes and cardiovascular disease. The plasma concentration ratio of TG/HDL-C has been proposed as a simple way to identify apparently healthy individuals at high cardio-metabolic risk. This study was carried out to compare the cardio-metabolic risk profiles of high-risk South Asian individuals identified by an elevated TG/HDL-C ratio versus those with a diagnosis of the metabolic syndrome. Methods: Body mass index, waist circumference, blood pressure, and fasting plasma glucose, insulin, TG, and HDL-C concentrations were determined in apparently healthy men (n=498) and women (n=526). The cardio-metabolic risk profile of “high risk” individuals identified by TG/HDL-C ratios in men (≥ 3.5) and women (≥2.5) was compared to those identified by a diagnosis of the metabolic syndrome. Results: More concentrations of all cardio-metabolic risk factors were significantly higher in “high risk” groups, identified by either the TG/HDL-C ratio or a diagnosis of the metabolic syndrome. TG, HDL-C, and insulin concentrations were not significantly different in “high risk” groups identified by either criterion, whereas plasma glucose and blood pressure were higher in those with the metabolic syndrome. Interpretation & conclusions: Apparently healthy South Asian individuals at high cardio-metabolic risk can be identified using either the TG/HDL-C ratio or the metabolic syndrome criteria. The TG/HDL-C ratio may be used as a simple marker to identify such individuals.

Adiposity and Cardiovascular Risk Clustering in South Asians

BACKGROUND South Asians have increased risk for type-2 diabetes and cardiovascular disease, but the relationship between metabolic health and weight has not been described. This study establishes the prevalence of metabolic abnormalities in normal weight, overweight, and obese South Asians. METHODS Participants were categorized by body mass index and waist circumference. Subjects with two or more cardiometabolic risk factors (blood pressure, glucose, insulin, triglycerides, high-density lipoprotein cholesterol, and C-reactive protein) were defined as metabolically abnormal. RESULTS Forty-one percent of the sample (n=1015) was metabolically abnormal, and 12% of those were normal weight. Of metabolically healthy individuals, 58% were overweight or obese. At a normal level of adiposity, women were more likely to be metabolically unhealthy, whereas men were more likely to be unhealthy with increasing adiposity. CONCLUSIONS Similar to other ethnic groups, a significant number of normal weight South Asians can be metabolically unhealthy.

MicroRNA associated with dyslipidemia and coronary disease in humans

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.

A review of the literature on the relationships between genetic polymorphisms and chemotherapy-induced nausea and vomiting

Despite current advances in antiemetic treatments, between 30% to and 60% of oncology patients experience chemotherapy-induced nausea (CIN) and 13% to 33% report chemotherapy-induced vomiting (CIV). Inter-individual differences are observed in the occurrence and severity of chemotherapy-induced nausea and vomiting (CINV). This review summarizes and critiques studies on associations between occurrence and severity of CINV and polymorphisms in serotonin receptor, drug metabolism, and drug transport pathway genes. Sixteen studies evaluated the associations between the occurrence and/or severity of CINV and single nucleotide polymorphisms (SNPs). Across these studies, three SNPs in 5-hydroxytryptamine receptor (5-HT3R) genes, two alleles of the cytochrome P450 family 2 subfamily D member 6 (CYP2D6) gene, and three SNPs in ATP binding cassette subfamily B member 1 (ABCB1) gene were associated with the occurrence and severity of CINV. Given the limited number of polymorphisms evaluated, additional research is warranted to identify new mechanisms to develop more targeted therapies.