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1.
J Acad Nutr Diet ; 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38215906

RESUMEN

BACKGROUND: Higher diet quality scores are associated with a lower risk for many chronic diseases and all-cause mortality; however, it is unclear if diet quality is associated with aging biology. OBJECTIVE: This study aimed to examine the association between diet quality and a measure of biological aging known as epigenetic aging. DESIGN: A cross-sectional data analysis was used to examine the association between three diet quality scores based on self-reported food frequency questionnaire data and five measures of epigenetic aging based on DNA methylation (DNAm) data from peripheral blood. PARTICIPANTS/SETTING: This study included 4,500 postmenopausal women recruited from multiple sites across the United States (1993-98), aged 50 to 79 years, with food frequency questionnaire and DNAm data available from the Women's Health Initiative baseline visit. MAIN OUTCOME MEASURES: Five established epigenetic aging measures were generated from HumanMethylation450 Beadchip DNAm data, including AgeAccelHannum, AgeAccelHorvath, AgeAccelPheno, AgeAccelGrim, and DunedinPACE. STATISTICAL ANALYSES PERFORMED: Linear mixed models were used to test for associations between three diet quality scores (Healthy Eating Index, Dietary Approaches to Stop Hypertension, and alternate Mediterranean diet scores) and epigenetic aging measures, adjusted for age, race and ethnicity, education, tobacco smoking, physical activity, Women's Health Initiative substudy from which DNAm data were obtained, and DNAm-based estimates of leukocyte proportions. RESULTS: Healthy Eating Index, Dietary Approaches to Stop Hypertension, and alternate Mediterranean diet scores were all inversely associated with AgeAccelPheno, AgeAccelGrim, and DunedinPACE (P < 0.05), with the largest effects with DunedinPACE. A one standard deviation increment in diet quality scores was associated with a decrement (ß ± SE) in DunedinPACE z score of -0.097 ± 0.014 (P = 9.70 x 10-13) for Healthy Eating Index, -0.107 ± 0.014 (P = 1.53 x 10-14) for Dietary Approaches to Stop Hypertension, and -0.068 ± 0.013 (P = 2.31 x 10-07) for the alternate Mediterranean diet. CONCLUSIONS: In postmenopausal women, diet quality scores were inversely associated with DNAm-based measures of biological aging, particularly DunedinPACE.

2.
Exp Clin Psychopharmacol ; 31(3): 715-723, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36107700

RESUMEN

Research on tobacco use disorder relies on a combination of self-reported use (e.g., cigarettes per day) and biochemical validation to quantify heaviness of use. However, electronic nicotine delivery system (ENDS) users may be unaware of how much they have vaped per day. The aim of this study was to test the relationship between self-reported heaviness of ENDS/tobacco use and nicotine biomarkers. Young adults (n = 30) who currently use ENDS and other tobacco products completed a detailed tobacco use history, timeline follow-back, and an ENDS topography session. We evaluated the self-reports of own-brand ENDS use and tested correlations to determine which self-report measures of own-brand use, and which self-reported measures of puff topography, had the strongest correlations with urine and/or blood biomarkers of nicotine use. Participants reported using a variety of different ENDS devices and had a range of usage. The sum of the self-reported number of occasions or hours of ENDS use, along with the number of cigarettes and other tobacco products used, over the past 24 hr was significantly correlated with plasma cotinine levels. Puff topography measures correlated with increased nicotine concentrations, although participants underestimated the number of puffs they took during the topography session. This study provides preliminary evidence that summing together the hours of ENDS use, or the number of occasions of ENDS use, in addition to the number of other tobacco products used (i.e., cigarettes) based on self-report may be an accurate method of quantification. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Productos de Tabaco , Adulto Joven , Humanos , Nicotina , Nicotiana , Autoinforme , Biomarcadores
3.
Epigenetics ; 17(3): 297-313, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-33818294

RESUMEN

Air pollution might affect atherosclerosis through DNA methylation changes in cells crucial to atherosclerosis, such as monocytes. We conducted an epigenome-wide study of DNA methylation in CD14+ monocytes and long-term ambient air pollution exposure in adults participating in the Multi-Ethnic Study of Atherosclerosis (MESA). We also assessed the association between differentially methylated signals and cis-gene expression. Using spatiotemporal models, one-year average concentrations of outdoor fine particulate matter (PM2.5) and oxides of nitrogen (NOX) were estimated at participants' homes. We assessed DNA methylation and gene expression using Illumina 450k and HumanHT-12 v4 Expression BeadChips, respectively (n = 1,207). We used bump hunting and site-specific approaches to identify differentially methylated signals (false discovery rate of 0.05) and used linear models to assess associations between differentially methylated signals and cis-gene expression. Four differentially methylated regions (DMRs) located on chromosomes 5, 6, 7, and 16 (within or near SDHAP3, ZFP57, HOXA5, and PRM1, respectively) were associated with PM2.5. The DMRs on chromosomes 5 and 6 also associated with NOX. The DMR on chromosome 5 had the smallest p-value for both PM2.5 (p = 1.4×10-6) and NOX (p = 7.7×10-6). Three differentially methylated CpGs were identified for PM2.5, and cg05926640 (near TOMM20) had the smallest p-value (p = 5.6×10-8). NOX significantly associated with cg11756214 within ZNF347 (p = 5.6×10-8). Several differentially methylated signals were also associated with cis-gene expression. The DMR located on chromosome 7 was associated with the expression of HOXA5, HOXA9, and HOXA10. The DMRs located on chromosomes 5 and 16 were associated with expression of MRPL36 and DEXI, respectively. The CpG cg05926640 was associated with expression of ARID4B, IRF2BP2, and TOMM20. We identified differential DNA methylation in monocytes associated with long-term air pollution exposure. Methylation signals associated with gene expression might help explain how air pollution contributes to cardiovascular disease.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Aterosclerosis , Adulto , Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/análisis , Contaminación del Aire/estadística & datos numéricos , Antígenos de Neoplasias/análisis , Aterosclerosis/inducido químicamente , Aterosclerosis/genética , Metilación de ADN , Exposición a Riesgos Ambientales/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Epigenoma , Humanos , Monocitos , Proteínas de Neoplasias , Material Particulado/toxicidad
4.
Commun Biol ; 4(1): 918, 2021 07 28.
Artículo en Inglés | MEDLINE | ID: mdl-34321601

RESUMEN

Long chain polyunsaturated fatty acids (LC-PUFAs) have critical signaling roles that regulate dyslipidemia and inflammation. Genetic variation in the FADS gene cluster accounts for a large portion of interindividual differences in circulating and tissue levels of LC-PUFAs, with the genotypes most strongly predictive of low LC-PUFA levels at strikingly higher frequencies in Amerind ancestry populations. In this study, we examined relationships between genetic ancestry and FADS variation in 1102 Hispanic American participants from the Multi-Ethnic Study of Atherosclerosis. We demonstrate strong negative associations between Amerind genetic ancestry and LC-PUFA levels. The FADS rs174537 single nucleotide polymorphism (SNP) accounted for much of the AI ancestry effect on LC-PUFAs, especially for low levels of n-3 LC-PUFAs. Rs174537 was also strongly associated with several metabolic, inflammatory and anthropomorphic traits including circulating triglycerides (TGs) and E-selectin in MESA Hispanics. Our study demonstrates that Amerind ancestry provides a useful and readily available tool to identify individuals most likely to have FADS-related n-3 LC-PUFA deficiencies and associated cardiovascular risk.


Asunto(s)
Ácido Graso Desaturasas/genética , Ácidos Grasos Omega-3/deficiencia , Variación Genética , Hispánicos o Latinos/genética , Indígenas Norteamericanos/genética , Familia de Multigenes , Ácido Graso Desaturasas/metabolismo , Herencia , Humanos , Estudios Longitudinales , Estados Unidos
5.
J Am Heart Assoc ; 10(12): e021118, 2021 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-34102851

RESUMEN

Background Although tobacco product use and transitions have been characterized in the general population, few studies have focused on individuals with established cardiovascular disease (CVD) in a population-based sample. Methods and Results We examined tobacco use prevalence and longitudinal patterns of tobacco product transitions in adults (≥18 years) of the nationally representative PATH (Population Assessment of Tobacco and Health) study, from 2013 to 2014 (Wave 1) through 2016 to 2018 (Wave 4). Prevalent CVD was classified through self-report of having had a heart attack, heart failure, stroke, or other heart condition. Factors associated with tobacco product use and transitions were investigated using survey logistic regression. We examined 2615 participants with self-reported CVD at Wave 1. Overall, 28.9% reported current tobacco use, equating to ≈6.2 million adults in the United States with prevalent CVD and current tobacco use. Among adults with CVD who are current tobacco users, the most commonly used product was cigarettes (82.8%), followed by any type of cigar (23.7%), and e-cigarette use (23.3%). E-cigarette use without concurrent cigarette use among participants with prevalent CVD was uncommon (1.1%). Factors associated with tobacco use were younger age, male sex, had lower education level, and lack of knowledge about the association between smoking and CVD. Men with prevalent CVD were less likely to use e-cigarettes compared with women (odds ratio [OR], 0.7; 95% CI, 0.5-0.9). Among cigarette users with CVD, transition rates between Waves 1 and 4 demonstrated <5% decrease in cigarette, with a 0.5% increase in e-cigarette use. Only ≈10% were in formal tobacco cessation programs. Conclusions Despite known harmful cardiovascular effects, over one fourth of adults with prevalent CVD use tobacco products and few quit smoking over the 4 waves of the PATH data set.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Sistemas Electrónicos de Liberación de Nicotina , Fumadores , Cese del Hábito de Fumar , Fumar/efectos adversos , Productos de Tabaco/efectos adversos , Adolescente , Adulto , Anciano , Enfermedades Cardiovasculares/diagnóstico , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Prevalencia , Medición de Riesgo , Factores de Riesgo , Fumar/epidemiología , Factores de Tiempo , Estados Unidos/epidemiología , Vapeo/efectos adversos , Vapeo/epidemiología , Adulto Joven
6.
Sci Rep ; 10(1): 15873, 2020 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-32985521

RESUMEN

Humans have undergone intense evolutionary selection to optimize their capacity to generate necessary quantities of long chain (LC-) polyunsaturated fatty acid (PUFA)-containing lipids. To better understand the impact of genetic variation within a locus of three FADS genes (FADS1, FADS2, and FADS3) on a diverse family of lipids, we examined the associations of 247 lipid metabolites (including four major classes of LC-PUFA-containing molecules and signaling molecules) with common and low-frequency genetic variants located within the FADS locus. Genetic variation in the FADS locus was strongly associated (p < 1.2 × 10-8) with 52 LC-PUFA-containing lipids and signaling molecules, including free fatty acids, phospholipids, lyso-phospholipids, and an endocannabinoid. Notably, the majority (80%) of FADS-associated lipids were not significantly associated with genetic variants outside of this FADS locus. These findings highlight the central role genetic variation at the FADS locus plays in regulating levels of physiologically critical LC-PUFA-containing lipids that participate in innate immunity, energy homeostasis, and brain development/function.


Asunto(s)
Ácido Graso Desaturasas/genética , Ácido Graso Desaturasas/metabolismo , Metabolismo de los Lípidos/genética , Metabolómica , delta-5 Desaturasa de Ácido Graso , Humanos , Polimorfismo de Nucleótido Simple
7.
Circ Genom Precis Med ; 13(4): e002766, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32525743

RESUMEN

BACKGROUND: DNA methylation patterns associated with habitual diet have not been well studied. METHODS: Diet quality was characterized using a Mediterranean-style diet score and the Alternative Healthy Eating Index score. We conducted ethnicity-specific and trans-ethnic epigenome-wide association analyses for diet quality and leukocyte-derived DNA methylation at over 400 000 CpGs (cytosine-guanine dinucleotides) in 5 population-based cohorts including 6662 European ancestry, 2702 African ancestry, and 360 Hispanic ancestry participants. For diet-associated CpGs identified in epigenome-wide analyses, we conducted Mendelian randomization (MR) analysis to examine their relations to cardiovascular disease risk factors and examined their longitudinal associations with all-cause mortality. RESULTS: We identified 30 CpGs associated with either Mediterranean-style diet score or Alternative Healthy Eating Index, or both, in European ancestry participants. Among these CpGs, 12 CpGs were significantly associated with all-cause mortality (Bonferroni corrected P<1.6×10-3). Hypermethylation of cg18181703 (SOCS3) was associated with higher scores of both Mediterranean-style diet score and Alternative Healthy Eating Index and lower risk for all-cause mortality (P=5.7×10-15). Ten additional diet-associated CpGs were nominally associated with all-cause mortality (P<0.05). MR analysis revealed 8 putatively causal associations for 6 CpGs with 4 cardiovascular disease risk factors (body mass index, triglycerides, high-density lipoprotein cholesterol concentrations, and type 2 diabetes mellitus; Bonferroni corrected MR P<4.5×10-4). For example, hypermethylation of cg11250194 (FADS2) was associated with lower triglyceride concentrations (MR, P=1.5×10-14).and hypermethylation of cg02079413 (SNORA54; NAP1L4) was associated with body mass index (corrected MR, P=1×10-6). CONCLUSIONS: Habitual diet quality was associated with differential peripheral leukocyte DNA methylation levels of 30 CpGs, most of which were also associated with multiple health outcomes, in European ancestry individuals. These findings demonstrate that integrative genomic analysis of dietary information may reveal molecular targets for disease prevention and treatment.


Asunto(s)
Enfermedades Cardiovasculares/genética , Metilación de ADN , Dieta Mediterránea , Leucocitos/metabolismo , Índice de Masa Corporal , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/patología , Islas de CpG , Ácido Graso Desaturasas/genética , Estudio de Asociación del Genoma Completo , Humanos , Proteínas Nucleares/genética , Factores de Riesgo , Proteína 3 Supresora de la Señalización de Citocinas/genética , Triglicéridos/sangre , Población Blanca/genética
8.
Epigenomics ; 11(13): 1487-1500, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31536415

RESUMEN

Aim: Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for in utero exposure in newborns is unknown. Materials & methods: We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and personal smoking (16 cohorts, 15907 participants, 2433 current smokers). Results & conclusion: Comparing meta-analyses, we identified numerous signatures specific to newborns along with many shared between newborns and adults. Unique smoking-associated genes in newborns were enriched in xenobiotic metabolism pathways. Our findings may provide insights into specific health impacts of prenatal exposure on offspring.


Asunto(s)
Metilación de ADN , Epigenómica/métodos , Efectos Tardíos de la Exposición Prenatal/genética , Fumar Tabaco/genética , Adulto , Estudios de Cohortes , Islas de CpG , Epigénesis Genética , Femenino , Humanos , Recién Nacido , Exposición Materna/efectos adversos , Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiología , Fumar Tabaco/epidemiología
9.
Diabetes ; 68(5): 1073-1083, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30936141

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D). We aimed to identify the peripheral blood DNA methylation signature of hepatic fat. We conducted epigenome-wide association studies of hepatic fat in 3,400 European ancestry (EA) participants and in 401 Hispanic ancestry and 724 African ancestry participants from four population-based cohort studies. Hepatic fat was measured using computed tomography or ultrasound imaging and DNA methylation was assessed at >400,000 cytosine-guanine dinucleotides (CpGs) in whole blood or CD14+ monocytes using a commercial array. We identified 22 CpGs associated with hepatic fat in EA participants at a false discovery rate <0.05 (corresponding P = 6.9 × 10-6) with replication at Bonferroni-corrected P < 8.6 × 10-4 Mendelian randomization analyses supported the association of hypomethylation of cg08309687 (LINC00649) with NAFLD (P = 2.5 × 10-4). Hypomethylation of the same CpG was also associated with risk for new-onset T2D (P = 0.005). Our study demonstrates that a peripheral blood-derived DNA methylation signature is robustly associated with hepatic fat accumulation. The hepatic fat-associated CpGs may represent attractive biomarkers for T2D. Future studies are warranted to explore mechanisms and to examine DNA methylation signatures of NAFLD across racial/ethnic groups.


Asunto(s)
Metilación de ADN/fisiología , Grasas/metabolismo , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Biomarcadores/metabolismo , Metilación de ADN/genética , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Humanos , Receptores de Lipopolisacáridos/metabolismo , Masculino , Persona de Mediana Edad , Factores de Riesgo
10.
Tob Control ; 28(1): 42-49, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-29574448

RESUMEN

BACKGROUND: The role of electronic cigarettes (e-cigarettes) in product transitions has been debated. METHODS: We used nationally representative data from the Population Assessment of Tobacco and Health Study waves 1 (2013-2014) and 2 (2014-2015) to investigate the associations between e-cigarette initiation and cigarette cessation/reduction in the USA. We limited the sample to current cigarette smokers aged 25+ years who were not current e-cigarette users at wave 1. We modelled 30-day cigarette cessation and substantial reduction in cigarette consumption as a function of e-cigarette initiation between surveys using multivariable logistic regression. RESULTS: Between waves 1 and 2, 6.9% of cigarette smokers who were not current e-cigarette users transitioned to former smokers. After adjusting for covariates, cigarette smokers who initiated e-cigarette use between waves and reported they used e-cigarettes daily at wave 2 had 7.88 (95% CI 4.45 to 13.95) times the odds of 30-day cigarette cessation compared with non-users of e-cigarettes at wave 2. Cigarette smokers who began using e-cigarettes every day and did not achieve cessation had 5.70 (95% CI 3.47 to 9.35) times the odds of reducing their average daily cigarette use by at least 50% between waves 1 and 2 compared with e-cigarette non-users. CONCLUSIONS: Daily e-cigarette initiators were more likely to have quit smoking cigarettes or reduced use compared with non-users. However, less frequent e-cigarette use was not associated with cigarette cessation/reduction. These results suggest incorporating frequency of e-cigarette use is important for developing a more thorough understanding of the association between e-cigarette use and cigarette cessation.


Asunto(s)
Fumar Cigarrillos/epidemiología , Sistemas Electrónicos de Liberación de Nicotina , Cese del Hábito de Fumar/estadística & datos numéricos , Vapeo/epidemiología , Adulto , Anciano , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Estados Unidos/epidemiología
11.
Environ Health Perspect ; 126(4): 047015, 2018 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-29706059

RESUMEN

BACKGROUND: Cigarette smoke is a causal factor in cancers and cardiovascular disease. Smoking-associated differentially methylated regions (SM-DMRs) have been observed in disease studies, but the causal link between altered DNA methylation and transcriptional change is obscure. OBJECTIVE: Our objectives were to finely resolve SM-DMRs and to interrogate the mechanistic link between SM-DMRs and altered transcription of enhancer noncoding RNA (eRNA) and mRNA in human circulating monocytes. METHOD: We integrated SM-DMRs identified by reduced representation bisulfite sequencing (RRBS) of circulating CD14+ monocyte DNA collected from two independent human studies [n=38 from Clinical Research Unit (CRU) and n=55 from the Multi-Ethnic Study of Atherosclerosis (MESA), about half of whom were active smokers] with gene expression for protein-coding genes and noncoding RNAs measured by RT-PCR or RNA sequencing. Candidate SM-DMRs were compared with RRBS of purified CD4+ T cells, CD8+ T cells, CD15+ granulocytes, CD19+ B cells, and CD56+ NK cells (n=19 females, CRU). DMRs were validated using pyrosequencing or bisulfite amplicon sequencing in up to 85 CRU volunteers, who also provided saliva DNA. RESULTS: RRBS identified monocyte SM-DMRs frequently located in putative gene regulatory regions. The most significant monocyte DMR occurred at a poised enhancer in the aryl-hydrocarbon receptor repressor gene (AHRR) and it was also detected in both granulocytes and saliva DNA. To our knowledge, we identify for the first time that SM-DMRs in or near AHRR, C5orf55-EXOC-AS, and SASH1 were associated with increased noncoding eRNA as well as mRNA in monocytes. Functionally, the AHRR SM-DMR appeared to up-regulate AHRR mRNA through activating the AHRR enhancer, as suggested by increased eRNA in the monocytes, but not granulocytes, from smokers compared with nonsmokers. CONCLUSIONS: Our findings suggest that AHRR SM-DMR up-regulates AHRR mRNA in a monocyte-specific manner by activating the AHRR enhancer. Cell type-specific activation of enhancers at SM-DMRs may represent a mechanism driving smoking-related disease. https://doi.org/10.1289/EHP2395.


Asunto(s)
Metilación de ADN/efectos de los fármacos , ARN Mensajero/efectos de los fármacos , ARN no Traducido/efectos de los fármacos , Fumar/efectos adversos , Sulfitos/efectos adversos , Transcripción Genética/efectos de los fármacos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismo , ARN no Traducido/metabolismo , Secuencias Reguladoras de Ácidos Nucleicos/efectos de los fármacos , Secuencias Reguladoras de Ácidos Nucleicos/genética
12.
J Am Heart Assoc ; 7(9)2018 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-29700041

RESUMEN

BACKGROUND: Characterizing electronic cigarette (e-cigarette) use patterns is important for guiding tobacco regulatory policy and projecting the future burden of tobacco-related diseases. Few studies have examined patterns of e-cigarette use in individuals with cardiovascular disease (CVD). METHODS AND RESULTS: We examined e-cigarette use in adults aged 18 to 89 years with a history of CVD, using data from the 2014 National Health Interview Survey. We investigated associations between ever and current e-cigarette use and smoking with multivariable logistic regression. In a secondary analysis, we modeled the association between e-cigarette use and a quit attempt over the past year. Former smokers with CVD who quit smoking within the past year showed 1.85 (95% confidence interval, 1.03, 3.33) times the odds of having ever used e-cigarettes as compared with those who reported being "some days" current smokers. Current smokers who attempted to quit smoking within the past year showed significantly increased odds of ever having used e-cigarettes (odds ratio, 1.70; 95% confidence interval, 1.25, 2.30) and currently using e-cigarettes (odds ratio, 1.97; 95% confidence interval, 1.32, 2.95) as compared with smokers who had not attempted to quit over the past year. CONCLUSIONS: Individuals with CVD who recently quit smoking or reported a recent quit attempt were significantly more likely to use e-cigarettes than current smokers and those who did not report a quit attempt. Our findings may indicate that this population is using e-cigarettes as an aid to smoking cessation. Characterizing emerging e-cigarette use behaviors in adults with CVD may help to inform outreach activities aimed at this high-risk population.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Sistemas Electrónicos de Liberación de Nicotina , Fumadores , Cese del Hábito de Fumar/métodos , Fumar Tabaco/prevención & control , Vapeo/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/terapia , Estudios Transversales , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Medición de Riesgo , Factores de Riesgo , Conducta de Reducción del Riesgo , Factores de Tiempo , Fumar Tabaco/efectos adversos , Fumar Tabaco/epidemiología , Fumar Tabaco/tendencias , Estados Unidos/epidemiología , Vapeo/efectos adversos , Vapeo/tendencias , Adulto Joven
13.
PLoS One ; 13(3): e0194610, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29590160

RESUMEN

Omega-6 (n-6) and omega-3 (n-3) long (≥ 20 carbon) chain polyunsaturated fatty acids (LC-PUFAs) play a critical role in human health and disease. Biosynthesis of LC-PUFAs from dietary 18 carbon PUFAs in tissues such as the liver is highly associated with genetic variation within the fatty acid desaturase (FADS) gene cluster, containing FADS1 and FADS2 that encode the rate-limiting desaturation enzymes in the LC-PUFA biosynthesis pathway. However, the molecular mechanisms by which FADS genetic variants affect LC-PUFA biosynthesis, and in which tissues, are unclear. The current study examined associations between common single nucleotide polymorphisms (SNPs) within the FADS gene cluster and FADS1 and FADS2 gene expression in 44 different human tissues (sample sizes ranging 70-361) from the Genotype-Tissue Expression (GTEx) Project. FADS1 and FADS2 expression were detected in all 44 tissues. Significant cis-eQTLs (within 1 megabase of each gene, False Discovery Rate, FDR<0.05, as defined by GTEx) were identified in 12 tissues for FADS1 gene expression and 23 tissues for FADS2 gene expression. Six tissues had significant (FDR< 0.05) eQTLs associated with both FADS1 and FADS2 (including artery, esophagus, heart, muscle, nerve, and thyroid). Interestingly, the identified eQTLs were consistently found to be associated in opposite directions for FADS1 and FADS2 expression. Taken together, findings from this study suggest common SNPs within the FADS gene cluster impact the transcription of FADS1 and FADS2 in numerous tissues and raise important questions about how the inverse expression of these two genes impact intermediate molecular (such a LC-PUFA and LC-PUFA-containing glycerolipid levels) and ultimately clinical phenotypes associated with inflammatory diseases and brain health.


Asunto(s)
Ácido Graso Desaturasas/genética , Ácidos Grasos Insaturados/metabolismo , Familia de Multigenes , Especificidad de Órganos , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , delta-5 Desaturasa de Ácido Graso , Regulación de la Expresión Génica , Genotipo , Humanos
14.
Epigenetics ; 12(12): 1092-1100, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29166816

RESUMEN

Alterations in DNA methylation and gene expression in blood leukocytes are potential biomarkers of harm and mediators of the deleterious effects of tobacco exposure. However, methodological issues, including the use of self-reported smoking status and mixed cell types have made previously identified alterations in DNA methylation and gene expression difficult to interpret. In this study, we examined associations of tobacco exposure with DNA methylation and gene expression, utilizing a biomarker of tobacco exposure (urine cotinine) and CD14+ purified monocyte samples from 934 participants of the community-based Multi-Ethnic Study of Atherosclerosis (MESA). Urine cotinine levels were measured using an immunoassay. DNA methylation and gene expression were measured with microarrays. Multivariate linear regression was used to test for associations adjusting for age, sex, race/ethnicity, education, and study site. Urine cotinine levels were associated with methylation of 176 CpGs [false discovery rate (FDR)<0.01]. Four CpGs not previously identified by studies of non-purified blood samples nominally replicated (P value<0.05) with plasma cotinine-associated methylation in 128 independent monocyte samples. Urine cotinine levels associated with expression of 12 genes (FDR<0.01), including increased expression of P2RY6 (Beta ± standard error = 0.078 ± 0.008, P = 1.99 × 10-22), a gene previously identified to be involved in the release of pro-inflammatory cytokines. No cotinine-associated (FDR<0.01) methylation profiles significantly (FDR<0.01) correlated with cotinine-associated (FDR<0.01) gene expression profiles. In conclusion, our findings i) identify potential monocyte-specific smoking-associated methylation patterns and ii) suggest that alterations in methylation may not be a main mechanism regulating gene expression in monocytes in response to cigarette smoking.


Asunto(s)
Metilación de ADN , Fumar Tabaco/genética , Anciano , Anciano de 80 o más Años , Aterosclerosis/epidemiología , Cotinina/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Fumar Tabaco/epidemiología , Fumar Tabaco/orina
15.
Nutrients ; 9(11)2017 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-29068398

RESUMEN

BACKGROUND: Dietary essential omega-6 (n-6) and omega-3 (n-3) 18 carbon (18C-) polyunsaturated fatty acids (PUFA), linoleic acid (LA) and α-linolenic acid (ALA), can be converted (utilizing desaturase and elongase enzymes encoded by FADS and ELOVL genes) to biologically-active long chain (LC; >20)-PUFAs by numerous cells and tissues. These n-6 and n-3 LC-PUFAs and their metabolites (ex, eicosanoids and endocannabinoids) play critical signaling and structural roles in almost all physiologic and pathophysiologic processes. METHODS: This review summarizes: (1) the biosynthesis, metabolism and roles of LC-PUFAs; (2) the potential impact of rapidly altering the intake of dietary LA and ALA; (3) the genetics and evolution of LC-PUFA biosynthesis; (4) Gene-diet interactions that may lead to excess levels of n-6 LC-PUFAs and deficiencies of n-3 LC-PUFAs; and (5) opportunities for precision nutrition approaches to personalize n-3 LC-PUFA supplementation for individuals and populations. CONCLUSIONS: The rapid nature of transitions in 18C-PUFA exposure together with the genetic variation in the LC-PUFA biosynthetic pathway found in different populations make mal-adaptations a likely outcome of our current nutritional environment. Understanding this genetic variation in the context of 18C-PUFA dietary exposure should enable the development of individualized n-3 LC-PUFA supplementation regimens to prevent and manage human disease.


Asunto(s)
Suplementos Dietéticos , Ácidos Grasos Omega-3/administración & dosificación , Enfermedades no Transmisibles/prevención & control , Dieta , Ácido Graso Desaturasas/sangre , Ácido Graso Desaturasas/genética , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-3/deficiencia , Ácidos Grasos Omega-6/administración & dosificación , Ácidos Grasos Omega-6/sangre , Ácidos Grasos Omega-6/deficiencia , Humanos , Inflamación/sangre , Inflamación/prevención & control , Ácido Linoleico/administración & dosificación , Ácido Linoleico/sangre , Estado Nutricional , Ácido alfa-Linolénico/administración & dosificación , Ácido alfa-Linolénico/sangre
16.
PLoS One ; 12(9): e0184914, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28922371

RESUMEN

To inform the study and regulation of emerging tobacco products, we sought to identify sensitive biomarkers of tobacco-induced subclinical cardiovascular damage by testing the cross-sectional associations of smoking with 17 biomarkers of inflammation in 2,702 GENOA study participants belonging to sibships ascertained on the basis of hypertension. Cigarette smoking was assessed by status, intensity (number of cigarettes per day), burden (pack-years of smoking), and time since quitting. We modeled biomarkers as geometric mean (GM) ratios using generalized estimating equations (GEE). The mean age of participants was 61 ±10 years; 64.5% were women and 54.4% African American. The prevalence of smoking was 12.2%. After adjusting for potential confounders, 6 of 17 biomarkers were significantly higher among current smokers at a Bonferroni adjusted p-value threshold (p<0.003). High sensitivity C-reactive protein was the most elevated biomarker among current smokers when compared to never smokers [GM ratio = 1.39 (95% CI: 1.23, 1.57); p <0.001]. Among former smokers, each pack-year of cigarettes smoked was associated with a 0.4% higher serum level of hsCRP [GM ratio = 1.004 (95% CI: 1.001, 1.006); p = 0.002] and each 5-year lapsed since quitting was associated with a 4% lower serum level of hsCRP [GM ratio = 0.96 (95% CI: 0.93, 0.99); p = 0.006]. However, we found no significant association of smoking intensity or burden with biomarkers of inflammation among current smokers. HsCRP appears to be the most sensitive biomarker of inflammation associated with cigarette smoking of those investigated, and could be a useful biomarker of smoking-related injury for the study and regulation of emerging tobacco products.


Asunto(s)
Proteína C-Reactiva/metabolismo , Fumar/sangre , Anciano , Biomarcadores/sangre , Femenino , Humanos , Inflamación/sangre , Inflamación/epidemiología , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Prevalencia , Fumar/epidemiología
17.
Nat Commun ; 8(1): 393, 2017 08 30.
Artículo en Inglés | MEDLINE | ID: mdl-28855511

RESUMEN

Little is known regarding the epigenetic basis of atherosclerosis. Here we present the CD14+ blood monocyte transcriptome and epigenome signatures associated with human atherosclerosis. The transcriptome signature includes transcription coactivator, ARID5B, which is known to form a chromatin derepressor complex with a histone H3K9Me2-specific demethylase and promote adipogenesis and smooth muscle development. ARID5B CpG (cg25953130) methylation is inversely associated with both ARID5B expression and atherosclerosis, consistent with this CpG residing in an ARID5B enhancer region, based on chromatin capture and histone marks data. Mediation analysis supports assumptions that ARID5B expression mediates effects of cg25953130 methylation and several cardiovascular disease risk factors on atherosclerotic burden. In lipopolysaccharide-stimulated human THP1 monocytes, ARID5B knockdown reduced expression of genes involved in atherosclerosis-related inflammatory and lipid metabolism pathways, and inhibited cell migration and phagocytosis. These data suggest that ARID5B expression, possibly regulated by an epigenetically controlled enhancer, promotes atherosclerosis by dysregulating immunometabolism towards a chronic inflammatory phenotype.The molecular mechanisms mediating the impact of environmental factors in atherosclerosis are unclear. Here, the authors examine CD14+ blood monocyte's transcriptome and epigenome signatures to find differential methylation and expression of ARID5B to be associated with human atherosclerosis.


Asunto(s)
Aterosclerosis/genética , Proteínas de Unión al ADN/genética , Monocitos/metabolismo , Factores de Transcripción/genética , Transcriptoma , Anciano , Aterosclerosis/metabolismo , Metilación de ADN , Proteínas de Unión al ADN/metabolismo , Epigénesis Genética , Femenino , Histonas/genética , Histonas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Monocitos/química , Factores de Transcripción/metabolismo
18.
Nicotine Tob Res ; 19(4): 442-451, 2017 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-27613907

RESUMEN

INTRODUCTION: Cigarette smoking is inversely associated with DNA methylation of the aryl hydrocarbon receptor repressor (AHRR; cg05575921). However, the association between secondhand tobacco smoke (SHS) exposure and AHRR methylation is unknown. METHODS: DNA methylation of AHRR cg05575921 in CD14+ monocyte samples, from 495 never-smokers and 411 former smokers (having quit smoking ≥15 years) from the Multi-Ethnic Study of Atherosclerosis (MESA), was cross-sectionally compared with concomitantly ascertained self-reported SHS exposure, urine cotinine concentrations, and estimates of air pollutants at participants' homes. Linear regression was used to test for associations, and covariates included age, sex, race, education, study site, and previous smoking exposure (smoking status, time since quitting, and pack-years). RESULTS: Recent indoor SHS exposure (hours per week) was inversely associated with cg05575921 methylation (ß ± SE = -0.009 ± 0.003, p = .007). The inverse effect direction was consistent (but did not reach significance) in the majority of stratified analyses (by smoking status, sex, and race). Categorical analysis revealed high levels of recent SHS exposure (≥10 hours per week) inversely associated with cg05575921 methylation (ß ± SE = -0.28 ± 0.09, p = .003), which remained significant (p < .05) in the majority of stratified analyses. cg05575921 methylation did not significantly (p < .05) associate with low to moderate levels of recent SHS exposure (1-9 hours per week), urine cotinine concentrations, years spent living with people smoking, years spent indoors (not at home) with people smoking, or estimated levels of air pollutants. CONCLUSIONS: High levels of recent indoor SHS exposure may be inversely associated with DNA methylation of AHRR in human monocytes. IMPLICATIONS: DNA methylation is a biochemical alteration that can occur in response to cigarette smoking; however, little is known about the effect of SHS on human DNA methylation. In the present study, we evaluated the association between SHS exposure and DNA methylation in human monocytes, at a site (AHRR cg05575921) known to have methylation inversely associated with current and former cigarette smoking compared to never smoking. Results from this study suggest high levels of recent SHS exposure inversely associate with DNA methylation of AHRR cg05575921 in monocytes from nonsmokers, albeit with weaker effects than active cigarette smoking.


Asunto(s)
Metilación de ADN/genética , Receptores de Hidrocarburo de Aril/genética , Contaminación por Humo de Tabaco , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Contaminación por Humo de Tabaco/análisis , Contaminación por Humo de Tabaco/estadística & datos numéricos
19.
Environ Health ; 15(1): 119, 2016 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-27903268

RESUMEN

BACKGROUND: DNA methylation may mediate effects of air pollution on cardiovascular disease. The association between long-term air pollution exposure and DNA methylation in monocytes, which are central to atherosclerosis, has not been studied. We investigated the association between long-term ambient air pollution exposure and DNA methylation (candidate sites and global) in monocytes of adults (aged ≥55). METHODS: One-year average ambient fine particulate matter (PM2.5) and oxides of nitrogen (NOX) concentrations were predicted at participants' (n = 1,207) addresses using spatiotemporal models. We assessed DNA methylation in circulating monocytes at 1) 2,713 CpG sites associated with mRNA expression of nearby genes and 2) probes mapping to Alu and LINE-1 repetitive elements (surrogates for global DNA methylation) using Illumina's Infinium HumanMethylation450 BeadChip. We used linear regression models adjusted for demographics, smoking, physical activity, socioeconomic status, methyl-nutrients, and technical variables. For significant air pollution-associated methylation sites, we also assessed the association between expression of gene transcripts previously associated with these CpG sites and air pollution. RESULTS: At a false discovery rate of 0.05, five candidate CpGs (cg20455854, cg07855639, cg07598385, cg17360854, and cg23599683) had methylation significantly associated with PM2.5 and none were associated with NOX. Cg20455854 had the smallest p-value for the association with PM2.5 (p = 2.77 × 10-5). mRNA expression profiles of genes near three of the PM2.5-associated CpGs (ANKHD1, LGALS2, and ANKRD11) were also significantly associated with PM2.5 exposure. Alu and LINE-1 methylation were not associated with long-term air pollution exposure. CONCLUSIONS: We observed novel associations between long-term ambient air pollution exposure and site-specific DNA methylation, but not global DNA methylation, in purified monocytes of a multi-ethnic adult population. Epigenetic markers may provide insights into mechanisms underlying environmental factors in complex diseases like atherosclerosis.


Asunto(s)
Contaminación del Aire/análisis , Metilación de ADN , Monocitos/metabolismo , Anciano , Anciano de 80 o más Años , Contaminantes Atmosféricos/análisis , Aterosclerosis , Población Negra , Islas de CpG , Femenino , Hispánicos o Latinos , Humanos , Masculino , Persona de Mediana Edad , Óxidos de Nitrógeno/análisis , Material Particulado/análisis , Transcriptoma , Estados Unidos , Población Blanca
20.
Circ Cardiovasc Genet ; 9(5): 436-447, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27651444

RESUMEN

BACKGROUND: DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders. METHODS AND RESULTS: To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15 907 blood-derived DNA samples from participants in 16 cohorts (including 2433 current, 6518 former, and 6956 never smokers). Comparing current versus never smokers, 2623 cytosine-phosphate-guanine sites (CpGs), annotated to 1405 genes, were statistically significantly differentially methylated at Bonferroni threshold of P<1×10-7 (18 760 CpGs at false discovery rate <0.05). Genes annotated to these CpGs were enriched for associations with several smoking-related traits in genome-wide studies including pulmonary function, cancers, inflammatory diseases, and heart disease. Comparing former versus never smokers, 185 of the CpGs that differed between current and never smokers were significant P<1×10-7 (2623 CpGs at false discovery rate <0.05), indicating a pattern of persistent altered methylation, with attenuation, after smoking cessation. Transcriptomic integration identified effects on gene expression at many differentially methylated CpGs. CONCLUSIONS: Cigarette smoking has a broad impact on genome-wide methylation that, at many loci, persists many years after smoking cessation. Many of the differentially methylated genes were novel genes with respect to biological effects of smoking and might represent therapeutic targets for prevention or treatment of tobacco-related diseases. Methylation at these sites could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke.


Asunto(s)
Metilación de ADN , Epigénesis Genética , Fumar/efectos adversos , Fumar/genética , Transcriptoma , Anciano , Estudios de Casos y Controles , Islas de CpG , Femenino , Perfilación de la Expresión Génica/métodos , Marcadores Genéticos , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Leucocitos/química , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Fumar/etnología , Cese del Hábito de Fumar , Prevención del Hábito de Fumar , Factores de Tiempo
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