Shared Environmental Influences on Electronic Cigarette Use Among Adolescent and Young Adult Females.

INTRODUCTION: Electronic cigarettes are now the most commonly used form of tobacco product among youth in the United States. Current evidence suggests that although e-cigarettes are perceived as less harmful and preferred over combustible cigarettes by adolescents, adolescents who try e-cigarettes are at greater risk of transitioning to combustible cigarettes. The genetic and environmental contributions to liability for e-cigarette use have not yet been examined using a behavioral genetic design. METHODS: Behavioral genetic models of lifetime and current e-cigarette use and friends who use e-cigarettes were examined among female monozygotic and dizygotic twins. RESULTS: A total of 41 female twin pairs (65.9% monozygotic twins; age = 19.7, SD = 1.6) with complete data on the study variables were included in the present analyses. The majority of the sample (68.1%) had at least some friends who use e-cigarettes. Additive genetic effects on e-cigarette use were not present, but the shared environment explained 98.7% of the variance in lifetime e-cigarette use, 96.6% in current e-cigarette use, and 94.9% in affiliation with friends who use e-cigarettes. CONCLUSION: This first study on the behavioral genetics of e-cigarette use among adolescents and young adults suggest that environmental factors shared by twins within a family seem to play a predominant role in the initial stages of e-cigarette use, a finding that is consistent with what has been found for tobacco. The findings emphasize the importance of continuing population-based tobacco control interventions to reduce the burden of e-cigarette use among adolescents. IMPLICATIONS: The shared environment significantly influences the initiation and regular use of electronic cigarettes and affiliation with friends who use electronic cigarettes among adolescent and young adult females. These findings underscore the importance of formulating preventive interventions that mitigate the social effects of familial influences on e-cigarette use through social skills training, education on harms of e-cigarettes for young people, or altering social norms regarding initiation of novel tobacco products.

The Genetic and Environmental Influences Contributing to the Association between Electronic and Conventional Cigarette Initiation.

INTRODUCTION: As the use of electronic cigarette (EC) continues to rise in the United States, especially among adolescents and young adults, it is necessary to better understand the factors associated with EC initiation. Specifically, it is unclear how genetic and environmental contributions influence the initiation of EC. Furthermore, the degree to which genetic and environmental influences are shared between EC initiation and conventional cigarette (CC) initiation is unknown. METHODS: A sample of young adult twins ages 15-20 (N = 858 individuals; 421 complete twin pairs) was used to estimate the genetic and environmental influences on the liability of initiation unique to EC and CC as well as the degree to which these factors are shared between the two. Approximately 24% of participants initiated the use of EC, 19% initiated the use of CC, and 11% initiated the dual use. RESULTS: Combined contributions of additive genetic and shared environmental influences were significant for CC (ACC = 0.19 [95% confidence interval {CI} = 0-0.79], p = 0.57; CCC = 0.42 [95% CI = 0-0.70], p = 0.13) and EC (AEC = 0.25 [95% CI = 0-0.83, p = 0.44; CEC = 0.42 [95% CI = 0-0.73], p = 0.12), whereas unique environmental influences were significant (ECC = 0.39 [95% CI = 0.18-0.57], p < 0.001; EEC = 0.32 [95% CI = 0.14-0.56], p < 0.001). Results also demonstrated a significant overlap of the unique environmental (rE = 0.87, p < 0.001) and familial influences contributing to correlation between the two phenotypes in the bivariate analysis. CONCLUSIONS: These preliminary results suggest that both genes and environmental influences are potential drivers of EC initiation among adolescents and young adults. IMPLICATIONS: This article is the first to use a sample of twin to estimate the contributions of genetic and environmental influences toward EC initiation and estimate the potential for overlapping influences with CC initiation. This study has implications for future debate about the etiology of EC and CC use with respect to potential overlapping genetic and environmental influences.

Differential plasma exosomal long non-coding RNAs expression profiles and their emerging role in E-cigarette users, cigarette, waterpipe, and dual smokers.

Long non-coding RNAs (lncRNAs) are the varied set of transcripts that play a critical role in biological processes like gene regulation, transcription, post-transcriptional modification, and chromatin remodeling. Recent studies have reported the presence of lncRNAs in the exosomes that are involved in regulating cell-to-cell communication in lung pathologies including lung cancer, chronic obstructive pulmonary disease (COPD), asthma, and idiopathic pulmonary fibrosis (IPF). In this study, we compared the lncRNA profiles in the plasma-derived exosomes amongst non-smokers (NS), cigarette smokers (CS), E-cig users (E-cig), waterpipe smokers (WP) and dual smokers (CSWP) using GeneChip™ WT Pico kit for transcriptional profiling. We found alterations in a distinct set of lncRNAs among subjects exposed to E-cig vapor, cigarette smoke, waterpipe smoke and dual smoke with some overlaps. Gene enrichment analyses of the differentially expressed lncRNAs demonstrated enrichment in the lncRNAs involved in crucial biological processes including steroid metabolism, cell differentiation and proliferation. Thus, the characterized lncRNA profiles of the plasma-derived exosomes from smokers, vapers, waterpipe users, and dual smokers will help identify the biomarkers relevant to chronic lung diseases such as COPD, asthma or IPF.

Replacing smoking with vaping during pregnancy: Impacts on metabolic health in mice.

Smoking is a significant risk factor for the development of metabolic diseases. Due to social pressures to quit smoking, many pregnant women are vaping as an alternative nicotine source. However, the metabolic consequences of replacing tobacco cigarettes with e-cigarettes during pregnancy are unknown. Therefore, in the mothers and their offspring, we investigated the metabolic and hepatic impacts of replacing cigarette smoke with e-vapour during pregnancy. Female BALB/c mice were either air-exposed or cigarette smoke-exposed (SE) from six weeks before pregnancy until lactation. At mating, a subset of the SE mice were instead exposed to e-vapour. Markers of glucose and lipid metabolism were measured in the livers and plasma, from the mothers and their male offspring (13 weeks). In the SE mothers, plasma insulin levels were reduced, leading to downstream increases in hepatic gluconeogenesis and plasma non-esterified fatty acids (NEFA). In the e-vapour replacement mothers, these changes were not as significant. In the SE offspring, there was impaired glucose tolerance, and increased plasma NEFA and liver triglyceride concentrations. E-vapour replacement restored lipid homeostasis but did not improve glucose tolerance. Therefore, in a murine model, low dose e-cigarette replacement during pregnancy is less toxic than cigarette smoke.

Personality Traits or Genetic Determinants-Which Strongly Influences E-Cigarette Users?

Presently, a growing popularity of electronic cigarettes may be observed. Used as a means of obtaining nicotine they allow to substitute traditional cigarettes. The origins of substance use disorders are conditioned by dopaminergic signaling which influences motivational processes being elementary factors conditioning the process of learning and exhibiting goal-directed behaviors. The study concentrated on analysis of three polymorphisms located in the dopamine receptor 2 (DRD2) gene-rs1076560, rs1799732 and rs1079597 using the PCR method, personality traits determined with the Big Five Questionnaire, and anxiety measured with the State Trait Anxiety Inventory. The study was conducted on a group of 394 volunteers, consisting e-cigarette users (n = 144) and controls (n = 250). Compared to the controls the case group subjects achieved significantly higher scores in regard to the STAI state and the trait scale, as well as the NEO-FFI Neuroticism and Openness scale. Likewise, in the case of the STAI state for DRD2 rs1076560 significant differences were found. Furthermore, while comparing the groups (e-cigarette users vs. controls) we noticed interactions for the NEO FFI Neuroticism and DRD2 rs1076560. The same was observed in the case of interactions significance while comparing groups (e-cigarette users vs. controls) for the STAI trait/scale and DRD2 rs1799732. Findings from this study demonstrate that psychological factors and genetic determinants should be analyzed simultaneously and comprehensively while considering groups of addicted patients. Since the use, and rapid increase in popularity, of electronic cigarettes has implications for public health, e-cigarette users should be studied holistically, especially younger groups of addicted and experimenting users.

Hypomethylation of LINE-1 repeat elements and global loss of DNA hydroxymethylation in vapers and smokers.

The outbreak of vaping-related severe lung injuries and deaths and the epidemic of teen vaping in the U.S. underscore the urgent need for determining the biological consequences of electronic cigarette (e-cig) use. We have investigated the association between vaping and epigenetic changes by quantifying DNA methylation levels in Long Interspersed Nucleotide Element 1 (LINE-1) and global DNA hydroxymethylation (5-hmC) levels and measuring the expression level of enzymes catalysing the respective processes in peripheral blood of exclusive vapers, smokers, and controls, matched for age, gender, and race (n = 45). Both vapers and smokers showed significant loss of methylation in LINE-1 repeat elements in comparison to controls (P = 0.00854 and P = 0.03078, respectively). Similarly, vapers and smokers had significant reductions in 5-hmC levels relative to controls (P = 0.04884 and P = 0.0035, respectively). Neither the LINE-1 methylation levels nor the global 5-hmC levels were different between vapers and smokers. There was a direct correlation between methylation levels in the LINE-1 elements and global 5-hmC levels in the study subjects (r = 0.31696, P = 0.03389). Inverse and statistically significant correlations were found between both the LINE-1 methylation levels and the global 5-hmC levels and various vaping/smoking metrics in the study subjects. There were modest but not statistically significant changes in transcription of DNA methyltransferases and ten-eleven translocation enzymes in both vapers and smokers relative to controls. Our findings support follow-up genome-wide investigations into the epigenetic effects of vaping, which may further clarify the health consequences of e-cig use. ABBREVIATIONS: 5-mC: 5-methylcytosine; 5-hmC: 5-hydroxymethylcytosine; 8-OHdG: 8-hydroxy-2'-deoxyguanosine; ACTIN: actin beta; ANOVA: Analysis of Variance; BER: base excision repair; BMI: body mass index; CO: carbon monoxide; COHb: carboxyhaemoglobin; COBRA: combined bisulphite restriction analysis; COPD: chronic obstructive pulmonary disease; DNMT1: DNA methyltransferase 1; DNMT3A: DNA methyltransferase 3A; DNMT3B: DNA methyltransferase 3B; e-cigs: electronic cigarettes; ELISA: enzyme-linked immunosorbent assay; ENDS: electronic nicotine delivery systems; FDA: Food and Drug Administration; GAPDH; glyceraldehyde-3-phosphate dehydrogenase; HPLC: high-performance liquid chromatography; LINE-1: Long Interspersed Nucleotide Element 1; PBS: phosphate-buffered saline; RFU: relative fluorescence units; RT-qPCR: quantitative reverse-transcription polymerase chain reaction; ROS: reactive oxygen species; SAM, S-adenosylmethionine; SE: standard error; TET1: ten-eleven translocation 1; TET2: ten-eleven translocation 2; TET3: ten-eleven translocation 3.