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1.
Int J Mol Sci ; 21(19)2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003475

RESUMO

The aim of this study was to identify placental DNA methylation (DNAm) variations associated with adiposity at 3 years of age. We quantified placental DNAm using the Infinium MethylationEPIC BeadChips. We assessed associations between DNAm at single-CpGs and skinfold thickness using robust linear regression models adjusted for gestational age, child's sex, age at follow-up and cellular heterogeneity. We sought replication of DNAm association with child adiposity in an independent cohort. We quantified placental mRNA levels for annotated gene using qRT-PCR and tested for correlation with DNAm. Lower DNAm at cg22593959 and cg22436429 was associated with higher adiposity (ß = -1.18, q = 0.002 and ß = -0.82, q = 0.04). The cg22593959 is located in an intergenic region (chr7q31.3), whereas cg22436429 is within the TFAP2E gene (1p34.3). DNAm at cg22593959 and cg22436429 was correlated with mRNA levels at FAM3C (rs = -0.279, p = 0.005) and TFAP2E (rs = 0.216, p = 0.03). In an independent cohort, the association between placental DNAm at cg22593959 and childhood adiposity was of similar strength and direction (ß = -3.8 ± 4.1, p = 0.36), yet non-significant. Four genomic regions were also associated with skinfold thickness within FMN1, MAGI2, SKAP2 and BMPR1B genes. We identified placental epigenetic variations associated with adiposity at 3 years of age suggesting that childhood fat accretion patterns might be established during fetal life.

2.
Diabetes ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051273

RESUMO

Hundreds of common genetic variants acting through distinguishable physiologic pathways influence the risk of type 2 diabetes (T2D). It is unknown to what extent the physiology underlying gestational diabetes (GDM) is distinct from that underlying T2D. In this study of over 5,000 pregnant women from three cohorts, we aimed to identify physiologically related groups of maternal variants associated with GDM using two complementary approaches based on Bayesian non-negative matrix factorization (bNMF) clustering. First, we tested five bNMF clusters of maternal T2D-associated variants grouped based on physiology outside of pregnancy for association with GDM. We found that cluster polygenic scores representing genetic determinants of reduced beta-cell function and abnormal hepatic lipid metabolism were associated with GDM; these clusters were not associated with infant birthweight. Second, we derived bNMF clusters of maternal variants based on pregnancy physiology and tested these clusters for association with GDM. We identified a cluster which was strongly associated with GDM and also associated with higher infant birthweight. The effect size for this cluster's association with GDM appeared greater than that for T2D. Our findings imply that the genetic and physiologic pathways that lead to GDM differ, at least in part, from those that lead to T2D.

3.
Am J Health Promot ; : 890117120928877, 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32515200

RESUMO

PURPOSE: To assess how nutrition knowledge is associated with global diet quality and to investigate whether sociodemographic characteristics (ie, sex, age, education, income, marital status, and living with children or not) moderate this association. DESIGN: Cross-sectional web-based study. PARTICIPANTS: The PREDISE study aims at identifying correlates of adherence to healthy eating guidelines in French-speaking adults from the Province of Quebec, Canada. SUBJECTS: A probability sample of 1092 participants (50% female). MEASURES: The Nutrition Knowledge Questionnaire and 24-hour food recalls from which the Canadian Healthy Eating Index (C-HEI) was calculated. ANALYSIS: Multiple linear regressions performed to assess how nutrition knowledge is associated with the C-HEI. Interaction terms tested to evaluate whether sociodemographic characteristics moderate the association between nutrition knowledge and the C-HEI. RESULTS: Nutrition knowledge (B = 0.141 [95% CI: 0.075-0.208], P < .0001) was identified as a significant correlate of the C-HEI. Education significantly moderated the association between nutrition knowledge and the C-HEI (P interaction = .0038), with a significative association among participants with a lower education level (B = 0.295 [95% CI: 0.170-0.421], P < .0001) but not among participants with a higher education level (B = 0.077 [95% CI: -0.004 to 0.157], P = .06). Whether participants lived with or without children also significantly moderated the association (P interaction = 0.0043); nutrition knowledge was associated with the C-HEI only in participants who were not living with children (B = 0.261 [95% CI: 0.167 to 0.355], P < .0001). CONCLUSION: This study suggests that the association between nutrition knowledge and adherence to healthy eating guidelines is not the same in different subgroups of the population. Interventions aiming at increasing nutrition knowledge may be a promising approach to improve diet quality, especially among individuals with a lower education.

4.
Biochim Biophys Acta Mol Basis Dis ; 1866(10): 165852, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32485219

RESUMO

MicroRNA (miRs) are small, non-coding RNA that post-transcriptionally regulate DNA expression. We hypothesized that specific miR profiles may be a feature of overactive osteoclasts in Paget's disease of bone (PDB), a disorder characterized by an increased and disorganized bone remodeling that typically begins with excessive bone resorption. We compared the expression profile of 13 miRs in human osteoclasts differentiated in vitro from peripheral blood mononuclear cells (PBMCs) of patients with PDB (n = 10) or age- and sex- matched healthy subjects (n = 10). We selected 13 miRs for testing, on the basis of their previously reported roles either in human osteoclast differentiation, in bone diseases, or in osteoclast important signaling pathways. From those expression results, 3 miRNAs were further selected for in-vitro studies aiming at modulating miR expression in human cord blood monocyte derived osteoclasts: 2 miRs (miR-146a-3p and miR-155-5p) whose expression was significantly reduced in pagetic osteoclasts, as well as miRNA-133a-3p, stable in PDB relative to controls, but with known regulatory importance within osteoclasts. We demonstrated a positive (miR-133a-3p) or negative (miR-155-5p, miR-146a-3p) impact of those miRs on the formation of osteoclasts and/or their bone resorption capacity in this human model. Signaling pathways were significantly affected, including p38 MAP-kinase (miR-133a-3p), RANKL-induced TRAF6/NFκB signaling (miR-146a-3p), and MITF expression (miR-155-5p). Osteoclast miRNA profiles might have an important value to yield significant new insights into the osteoclast phenotype in PDB and in other bone diseases with hyperactive osteoclasts.

5.
Pediatr Obes ; 15(8): e12642, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32351036

RESUMO

BACKGROUND: Introducing complementary foods other than breastmilk or formula acutely changes the infant gut microbiota composition. However, it is unknown whether the timing of introduction to complementary foods (early vs. late) in infancy is associated with early childhood gut microbiota and BMI, and if these associations depend on breastfeeding duration. OBJECTIVE: Our primary objective was to investigate whether timing of infant complentary feeding with solid foods is associated with early childhood gut microbiota composition and BMI-z, and whether these associations differ by duration of breastfeeding. METHODS: We used data from a Canadian pre-birth cohort followed till age 5 years. We examined timing of introduction to solid foods with the gut microbiota, determined by 16S rRNA gene sequencing of stool collected at 5 years of age, and age-and-sex specific BMI-z. We conducted analyses before and after stratifying by breastfeeding duration, and adjusted for delivery mode, gestational age and birth weight. RESULTS: Of the 392 children in the analysis, 109 (27.8%) had early (≤4 months) solids. The association between early (vs later) solids and BMI-z at 5 years was modified by breastfeeding status at 4 months (P = .06). Among children breastfed >4 months, early (vs later) solids were associated with differential relative abundance of 6 bacterial taxa, including lower Roseburia, and 0.30 higher BMI-z (95% CI: 0.05, 0.55) at 5 years. In children breastfed <4 months, early solids were associated with differential relative abundance of 9 taxa, but not with child BMI-z. CONCLUSIONS: Early (vs. later) introduction to solid foods in infancy is associated with altered gut microbiota composition and BMI in early childhood, however these associations differ by duration of breastfeeding.

6.
Genome Med ; 12(1): 25, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32114984

RESUMO

BACKGROUND: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. METHODS: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. RESULTS: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. CONCLUSIONS: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.

7.
Int J Mol Sci ; 21(1)2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31947745

RESUMO

Changes in fetal DNA methylation (DNAm) of the leptin (LEP) gene have been associated with exposure to maternal hyperglycemia, but their links with childhood obesity risk are still unclear. We investigated the association between maternal hyperglycemia, placental LEP DNAm (25 5'-C-phosphate-G-3' (CpG) sites), neonatal leptinemia, and adiposity (i.e., BMI and skinfold thickness (ST) (subscapular (SS) + triceps (TR) skinfold measures, and the ratio of SS:TR) at 3-years-old, in 259 mother-child dyads, from Gen3G birth cohort. We conducted multivariate linear analyses adjusted for gestational age at birth, sex of the child, age at follow-up, and cellular heterogeneity. We assessed the causal role of DNAm in the association between maternal glycemia and childhood outcomes, using mediation analysis. We found three CpGs associated with neonatal leptinemia (p ≤ 0.002). Of these, cg05136031 and cg15758240 were also associated with BMI (ß = -2.69, p = 0.05) and fat distribution (ß = -0.581, p = 0.05) at 3-years-old, respectively. Maternal glycemia was associated with DNAm at cg15758240 (ß = -0.01, p = 0.04) and neonatal leptinemia (ß = 0.19, p = 0.004). DNAm levels at cg15758240 mediates 0.8% of the association between maternal glycemia and neonatal leptinemia (p < 0.001). Our results support that DNAm regulation of the leptin pathway in response to maternal glycemia might be involved in programming adiposity in childhood.


Assuntos
Metilação de DNA , Diabetes Gestacional/genética , Hiperglicemia/genética , Leptina/genética , Obesidade/etiologia , Adiposidade , Adulto , Pré-Escolar , Diabetes Gestacional/metabolismo , Epigênese Genética , Feminino , Sangue Fetal/metabolismo , Loci Gênicos , Humanos , Hiperglicemia/metabolismo , Recém-Nascido , Leptina/metabolismo , Masculino , Obesidade/genética , Obesidade/metabolismo , Placenta/metabolismo , Gravidez , Adulto Jovem
8.
Sleep Med ; 65: 54-61, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31710875

RESUMO

BACKGROUND: Women with high levels of physical activity (PA) are less likely to develop gestational diabetes mellitus (GDM), but the relations with sleep and sedentary behaviours (SB) are more controversial. We aimed to investigate all three components (sleep, PA, and SB) and their association with maternal glucose in pregnancy. METHODS: We included 766 pregnant women recruited at first trimester and that we followed at second trimester. We collected blood samples, anthropometry and standardized questionnaires about lifestyle including PA, SB, and sleep duration at both visits. Women completed a 50 g glucose challenge test at first trimester and 75-g oral glucose tolerance test (OGTT) at second trimester. We conducted regression analyses to test cross-sectional associations between sleep, PA, and SB with maternal glucose levels while taking into account potential confounders (maternal age, pre-pregnancy body mass index (BMI), gravidity, and smoking). We considered linear and quadratic relationships. RESULTS: At first trimester, we observed a linear relationship between shorter sleep duration and higher glucose levels, which was attenuated after adjustments for confounders. At second trimester, we found a quadratic relationship between sleep and glucose showing lowest levels at fasting and 1 h-post OGTT for women who slept 6-10 h/night. This association remained significant after adjusting for confounders and taking into account PA and/or SB. Greater amount of SB was associated with higher 1 h-glucose after adjustment for confounders (ß = 0.132; SE = 0.047; P = 0.005). CONCLUSIONS: Sleep duration is associated with glucose regulation in pregnancy, independently of PA and SB, and this association varies according to the period of gestation.

9.
Diabetes ; 69(3): 484-492, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31882564

RESUMO

The placenta participates in maternal insulin sensitivity changes during pregnancy; however, mechanisms remain unclear. We investigated associations between maternal insulin sensitivity and placental DNA methylation markers across the genome. We analyzed data from 430 mother-offspring dyads in the Gen3G cohort. All women underwent 75-g oral glucose tolerance tests at ∼26 weeks of gestation; we used glucose and insulin measures to estimate insulin sensitivity (Matsuda index). At delivery, we collected samples from placenta (fetal side) and measured DNA methylation using Illumina EPIC arrays. Using linear regression models to quantify associations at 720,077 cytosine-guanine dinucleotides (CpGs), with adjustment for maternal age, gravidity, smoking, BMI, child sex, and gestational age at delivery, we identified 188 CpG sites where placental DNA methylation was associated with Matsuda index (P < 6.94 × 10-8). Among genes annotated to these 188 CpGs, we found enrichment in targets for miRNAs, in histone modifications, and in parent-of-origin DNA methylation including the H19/MIR675 locus (paternally imprinted). We identified 12 known placenta imprinted genes, including KCNQ1 Mendelian randomization analyses revealed five loci where placenta DNA methylation may causally influence maternal insulin sensitivity, including the maternally imprinted gene DLGAP2. Our results suggest that placental DNA methylation is fundamentally linked to the regulation of maternal insulin sensitivity in pregnancy.


Assuntos
Glicemia/metabolismo , Metilação de DNA , Diabetes Gestacional/genética , Resistência à Insulina/genética , Insulina/metabolismo , Placenta/metabolismo , Gravidez/metabolismo , Adulto , Peso ao Nascer , Ilhas de CpG , Diabetes Gestacional/metabolismo , Feminino , Impressão Genômica , Teste de Tolerância a Glucose , Humanos , Recém-Nascido , Canal de Potássio KCNQ1/genética , Modelos Lineares , Masculino , Análise da Randomização Mendeliana , MicroRNAs/genética , Proteínas do Tecido Nervoso/genética , RNA Longo não Codificante/genética
10.
Nutrients ; 11(12)2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31842253

RESUMO

The objectives were to assess whether social support for healthy eating and perceived food environment are associated with diet quality, and to investigate if sociodemographic characteristics moderate these associations. A probability sample of French-speaking adults from the Province of Québec, Canada, was recruited in the context of the PREDISE study. Participants reported their perceptions of supportive and non-supportive actions related to healthy eating from close others at home and outside of home (n = 952), and of the accessibility to healthy foods (n = 1035). The Canadian Healthy Eating Index (C-HEI) was calculated based on three Web-based 24 h food recalls. Multiple linear regression models showed that supportive (B = 1.50 (95% CI 0.46, 2.54)) and non-supportive (B = -3.06 (95% CI -4.94, -1.18)) actions related to healthy eating from close others at home were positively and negatively associated with C-HEI, respectively, whereas actions from close others outside of home were not. The negative association between non-supportive actions occurring at home and C-HEI was stronger among participants with lower (vs. higher) levels of education (p interaction = 0.03). Perceived accessibility to healthy foods was not associated with C-HEI (p > 0.05). These results suggest that the social environment may have a stronger influence on healthy eating than the perceived physical environment. This adds support for healthy eating promotion programs involving entire families, especially for more socioeconomically disadvantaged individuals, whose efforts to eat healthily may be more easily thwarted by non-supportive households.


Assuntos
Dieta Saudável/estatística & dados numéricos , Dieta/psicologia , Comportamento Alimentar/psicologia , Abastecimento de Alimentos , Apoio Social , Adolescente , Adulto , Idoso , Inquéritos sobre Dietas , Meio Ambiente , Características da Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção , Quebeque , Adulto Jovem
11.
J Dev Orig Health Dis ; : 1-10, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31753053

RESUMO

Placental lipids transfer is essential for optimal fetal development, and alterations of these mechanisms could lead to a higher risk of adverse birth outcomes. Low-density lipoprotein receptor (LDLR), LDL receptor-related protein 1 (LRP1), and scavenger receptor class B type 1 (SCARB1) genes are encoding lipoprotein receptors expressed in the placenta where they participate in cholesterol exchange from maternal to fetal circulation. The aim of this study was thus to investigate the association between maternal lipid changes occurring in pregnancy, placental DNA methylation (DNAm) variations at LDLR, LRP1, and SCARB1 gene loci, and newborn's anthropometric profile at birth. Sixty-nine normoglycemic women were followed from the first trimester of pregnancy until delivery. Placental DNAm was quantified at 43 Cytosine-phosphate-Guanines (CpGs) at LDLR, LRP1, and SCARB1 gene loci using pyrosequencing: 4 CpGs were retained for further analysis. Maternal clinical data were collected at each trimester of pregnancy. Newborns' data were collected from medical records. Statistical models included minimally newborn sex and gestational and maternal age. Maternal total cholesterol changes during pregnancy (ΔT3-T1) were correlated with DNAm variations at LDLR (r = -0.32, p = 0.01) and LRP1 (r = 0.34, p = 0.007). DNAm at these loci was also correlated with newborns' cord blood triglyceride and leptin levels. Mediation analysis supports a causal relationship between maternal cholesterol changes, DNAm levels at LRP1 locus, and cord blood leptin concentration (pmediation = 0.02). These results suggest that LRP1 DNAm link maternal blood cholesterol changes in pregnancy and offspring adiposity at birth, which provide support for a better follow-up of blood lipids in pregnancy.

12.
Am J Epidemiol ; 188(11): 1878-1886, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31497855

RESUMO

Prenatal maternal smoking is a risk factor for lower birth weight. We performed epigenome-wide association analyses of placental DNA methylation (DNAm) at 720,077 cytosine-phosphate-guanine (CpG) sites and prenatal maternal smoking among 441 mother-infant pairs (2010-2014) and evaluated whether DNAm mediates the association between smoking and birth weight using mediation analysis. Mean birth weight was 3,443 (standard deviation, 423) g, and 38 mothers (8.6%) reported smoking at a mean of 9.4 weeks of gestation. Prenatal maternal smoking was associated with a 175-g lower birth weight (95% confidence interval (CI): -305.5, -44.8) and with differential DNAm of 71 CpGs in placenta, robust to latent-factor adjustment reflecting cell types (Bonferroni-adjusted P < 6.94 × 10-8). Of the 71 CpG sites, 7 mediated the association between prenatal smoking and birth weight (on MDS2, PBX1, CYP1A2, VPRBP, WBP1L, CD28, and CDK6 genes), and prenatal smoking × DNAm interactions on birth weight were observed for 5 CpG sites. The strongest mediator, cg22638236, was annotated to the PBX1 gene body involved in skeletal patterning and programming, with a mediated effect of 301-g lower birth weight (95% CI: -543, -86) among smokers but no mediated effect for nonsmokers (ß = -38 g; 95% CI: -88, 9). Prenatal maternal smoking might interact with placental DNAm at specific loci, mediating the association with lower infant birth weight.


Assuntos
Peso ao Nascer , Metilação de DNA , Placenta/metabolismo , Fumar/metabolismo , Adulto , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Adulto Jovem
13.
Neurol Genet ; 5(3): e338, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31334355

RESUMO

Objective: To assess the effects of dystrophia myotonica protein kinase (DMPK) DNA methylation (DNAme) epivariation on muscular and respiratory profiles in patients with myotonic dystrophy type 1 (DM1). Methods: Phenotypes were assessed with standardized measures. Pyrosequencing of bisulfite-treated DNA was used to quantify DNAme levels in blood from 90 patients with DM1 (adult form). Modal CTG repeat length was assessed using small-pool PCR. The presence of Acil-sensitive variant repeats was also tested. Results: DNAme levels upstream of the CTG expansion (exon and intron 11) were correlated with modal CTG repeat length (rs = -0.224, p = 0.040; rs = -0.317, p = 0.003; and rs = -0.241, p = 0.027), whereas correlations were observed with epivariations downstream of the CTG repeats (rs = 0.227; p = 0.037). The presence of a variant repeat was associated with higher DNAme levels at multiple CpG sites (up to 10% higher; p = 0.001). Stepwise multiple linear regression modeling showed that DNAme contributed significantly and independently to explain phenotypic variability in ankle dorsiflexor (3 CpGs: p = 0.001, 0.013, and 0.001), grip (p = 0.089), and pinch (p = 0.028) strengths and in forced vital capacity (2 CpGs: p = 0.002 and 0.021) and maximal inspiratory pressure (p = 0.012). Conclusions: In addition to the CTG repeat length, DMPK epivariations independently explain phenotypic variability in DM1 and could thus improve prognostic accuracy for patients.

14.
Epigenetics ; 14(12): 1177-1182, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31250700

RESUMO

Illumina HumanMethylation450 BeadChip (450K) has been commonly used to investigate DNA methylation in human tissues. Recently, it has been replaced by Illumina HumanMethylationEPIC BeadChip (EPIC) covering over 850,000 CpGs distributed genome-wide. Many consortia have now datasets coming from both arrays and aspire to analyze the two together. The placenta shows a high number of intermediate methylation levels and is often investigated for obstetric/birth outcomes, and potentially for long-term programming in offspring. We performed a systematic comparison between the two arrays using 108 duplicate placental samples from Gen3G birth cohort. We find that placenta shows a high per-sample correlation between the arrays, and higher median correlations at individual CpGs than those reported for blood. We identify 26,340 probes with absolute difference in per cent methylation >10%. We conclude that EPIC and 450K placental data can be combined, and we provide two lists of CpGs that should be excluded to avoid misleading results.

15.
Hum Mol Genet ; 28(13): 2245-2254, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31220271

RESUMO

Myotonic dystrophy type 1 (DM1) is an autosomal dominant inherited disorder caused by expansion of a germline and somatically unstable CTG repeat in the DMPK gene. Previously, CTG repeat length at birth has been correlated to patient age at symptom onset. Attempts to correlate CTG repeat length with progressive DM1 phenotypes, such as muscle power, have proven difficult. To better correlate genotype with progressive phenotypes, we have measured CTG repeat tract length and screened for interrupting variant repeats in 192 study participants from a well-characterized Canadian cohort. We have assessed genotype-phenotype correlations with nine progressive measures of skeletal muscle power and respiratory function. We have built statistical models that include confounding factors such as sex, age, height and weight to further explain variation in muscle power. Our analysis reveals a strong correlation between DM1 genotype and respiratory function and skeletal muscle power, as part of a complex model that includes additional modulators such as sex, age, height, weight and the presence or absence of interrupting variant repeats. Distal skeletal muscle measurements, such as hand pinch and grip strength, show the strongest correlation with disease genotype. Detailed analysis of CTG repeat length, and incorporation of confounding factors, greatly improves the predictive ability of these models. They reveal a greater genetic influence on individual progressive phenotypes than on age at symptom onset and for clinical trials will help optimize stratification and explain patient variability. They will also help practitioners prioritize assessment of the muscular power measurements that correlate best with disease severity.


Assuntos
Músculo Esquelético/fisiopatologia , Distrofia Miotônica/genética , Miotonina Proteína Quinase/genética , Expansão das Repetições de Trinucleotídeos , Alelos , Canadá , Estudos de Coortes , Feminino , Estudos de Associação Genética , Genótipo , Força da Mão/fisiologia , Humanos , Masculino , Modelos Estatísticos , Distrofia Miotônica/fisiopatologia , Fenótipo , Testes de Função Respiratória
16.
Epigenomics ; 11(8): 917-934, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31144512

RESUMO

Aim: To comprehensively characterize the high-density lipoproteins (HDLs) microtranscriptome and to assess whether it is distinct from that of plasma and different between women and men. Methods: RNA was extracted from ultracentrifugation-purified HDLs and plasma from 17 healthy women and men couples, and libraries were sequenced on a HiSeq2500 platform. Results: On average, 310 ± 64 and 355 ± 31 miRNAs were detected (≥1 read per million) in HDLs and plasma, respectively. A total of 62 and 134 miRNAs were over-represented (e.g., miR-150-5p; fold change = 7.52; padj = 5.41 × 10-111) and under-represented (e.g., miR-22-3p; fold change = -5.28; padj = 2.11 × 10-154) in HDLs compared with plasma. These miRNAs were enriched in lipid metabolism and cellular processes-related pathways. Conclusion: HDLs exhibit a sex-independent miRNA profile distinct from that of plasma. These miRNAs may contribute to the HDLs' physiology.

17.
Epigenetics ; 14(4): 405-420, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30885044

RESUMO

DNA methylation is known to be responsive to prenatal exposures, which may be a part of the mechanism linking early developmental exposures to future chronic diseases. Many studies use blood to measure DNA methylation, yet we know that DNA methylation is tissue specific. Placenta is central to fetal growth and development, but it is rarely feasible to collect this tissue in large epidemiological studies; on the other hand, cord blood samples are more accessible. In this study, based on paired samples of both placenta and cord blood tissues from 169 individuals, we investigated the methylation concordance between placenta and cord blood. We then employed a machine-learning-based model to predict locus-specific DNA methylation levels in placenta using DNA methylation levels in cord blood. We found that methylation correlation between placenta and cord blood is lower than other tissue pairs, consistent with existing observations that placenta methylation has a distinct pattern. Nonetheless, there are still a number of CpG sites showing robust association between the two tissues. We built prediction models for placenta methylation based on cord blood data and documented a subset of 1,012 CpG sites with high correlation between measured and predicted placenta methylation levels. The resulting list of CpG sites and prediction models could help to reveal the loci where internal or external influences may affect DNA methylation in both placenta and cord blood, and provide a reference data to predict the effects on placenta in future study even when the tissue is not available in an epidemiological study.

18.
Can J Physiol Pharmacol ; 97(3): 147-154, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30661367

RESUMO

Childhood obesity is a predictor of adult obesity and has its roots in the pre-pregnancy or pregnancy period. This review presents an overview of the prenatal risk factors for childhood obesity, which were categorized into 2 groups: biological risk factors (maternal pre-pregnancy body mass index, gestational weight gain, diabetes in pregnancy, and caesarean section), and environmental and behavioural risk factors (maternal smoking and exposure to obesogens, maternal dietary patterns, maternal intestinal microbiome and antibiotics exposure, and maternal psychosocial stress). Identifying modifiable predisposing prenatal factors for obesity will inform further development of inventions to prevent obesity over the life course, and future directions for research and intervention are discussed.


Assuntos
Obesidade Pediátrica/etiologia , Animais , Feminino , Humanos , Gravidez , Complicações na Gravidez/etiologia , Fatores de Risco
19.
Metabolism ; 91: 39-42, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30468781

RESUMO

AIM: To characterize lipid profiles in women with different gestational diabetes mellitus (GDM) physiologic subtypes. METHODS: We measured seven lipid markers (total cholesterol, LDL, HDL, triglycerides, non-esterified fatty acids (NEFA), ApoA, ApoB) in fasting plasma collected in a prospective cohort of 805 pregnant women during second trimester. We estimated insulin sensitivity and secretion using oral glucose tolerance test-based validated indices. We categorized GDM physiologic subtypes by insulin sensitivity and secretion defects defined as values below the 25th percentile among women with normal glucose tolerance (NGT), as previously established. We compared lipid markers across NGT and GDM subtypes. We explored associations between lipid markers and newborn anthropometry in the overall group and stratified by glucose tolerance status. RESULTS: Among 805 women, 67 (8.3%) developed GDM. Women with GDM had higher body mass index (BMI; 29.3 vs. 26.6 kg/m2), while ethnicity (97.3% vs. 97.0% European ancestry) and age (28 vs. 29 years) were similar. In comparison to women with NGT, women with GDM characterized by a predominant insulin sensitivity defect had significantly higher triglycerides (2.20 vs. 1.82, P = 0.002), lower HDL (1.64 vs. 1.90, P = 0.01) and higher NEFA (0.34 vs. 0.24, P < 0.0001). GDM women with a predominant insulin secretion defect differed from women with NGT with respect to NEFA (0.32 vs. 0.24, P = 0.003) while other lipid markers were similar. These associations remained significant after adjusting for maternal age and BMI. Greater maternal levels of NEFA were associated with higher birth weight z-scores in women with an insulin secretion defect (BMI-adjusted r = 0.58, P = 0.01). We did not find significant associations between other lipid markers and newborn anthropometry in other groups. CONCLUSION: Women with GDM have distinct lipid profiles based on their GDM physiologic subtype which may not be apparent when investigating GDM as a single group.


Assuntos
Diabetes Gestacional/metabolismo , Metabolismo dos Lipídeos , Adulto , Biomarcadores/sangue , Peso ao Nascer , Índice de Massa Corporal , Estudos de Coortes , Diabetes Gestacional/fisiopatologia , Grupos Étnicos , Feminino , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina , Lipídeos/sangue , Idade Materna , Gravidez , Estudos Prospectivos , Adulto Jovem
20.
Can J Cardiol ; 34(12): 1665-1673, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30527156

RESUMO

BACKGROUND: Regular monitoring of the population's food and nutrient intake is essential to develop effective nutrition-focused public health policies. The aim of this study was to provide dietary intake estimates using an age- and sex-representative sample of French-speaking adults with Internet access from 5 administrative regions in the province of Quebec, Canada. METHODS: PRÉDicteurs Individuels, Sociaux et Environnementaux (PREDISE) is a multicentre cross-sectional study that used a Web-based approach to collect individual, social, and environmental data on factors associated with adherence to dietary recommendations. Dietary intake was estimated from the average of 3 validated Web-based 24-hour recalls. RESULTS: Mean (± SD) age of the 1147 participants (50.2% women) was 43.2 ± 4.6 years and median body mass index was 26.3 (interquartile range, 23.3-30.3). Less than 25% of participants met Canada's Food Guide recommendations for vegetables and fruit intake (prevalence, 23.6%; 95% confidence interval [CI], 21.1-26.0). Most participants reported consuming more than 2300 mg of sodium (prevalence, 80.5%; 95% CI, 78.2-82.7) and more than 10% energy as saturated fats (prevalence, 74.2%; 95% CI, 71.6-76.7). Mean Canadian Healthy Eating Index score on a scale of 0-100 was 54.5 (95% CI, 53.8-55.2), reflecting relatively poor diet quality according to current dietary recommendations. CONCLUSIONS: Self-reported dietary intakes measured using a new validated Web-based 24-hour recall in this sample of French-speaking adults from Quebec and with access to Internet suggest low adherence to current Canadian dietary guidelines. These data emphasize the need for more effective nutrition-focused public health policies to maximize cardiovascular disease prevention at the population level.


Assuntos
Inquéritos sobre Dietas , Comportamento Alimentar , Política Nutricional , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Estudos Transversais , Escolaridade , Feminino , Humanos , Renda , Masculino , Pessoa de Meia-Idade , Quebeque/epidemiologia , Autorrelato , Fatores Sexuais , Adulto Jovem
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