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2.
PLoS Biol ; 18(9): e3000870, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32986697

RESUMO

Obesity and related metabolic diseases show clear sex-related differences. The growing burden of these diseases calls for better understanding of the age- and sex-related metabolic consequences. High-throughput lipidomic analyses of population-based cohorts offer an opportunity to identify disease-risk-associated biomarkers and to improve our understanding of lipid metabolism and biology at a population level. Here, we comprehensively examined the relationship between lipid classes/subclasses and molecular species with age, sex, and body mass index (BMI). Furthermore, we evaluated sex specificity in the association of the plasma lipidome with age and BMI. Some 747 targeted lipid measures, representing 706 molecular lipid species across 36 classes/subclasses, were measured using a high-performance liquid chromatography coupled mass spectrometer on a total of 10,339 participants from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab), with 563 lipid species being validated externally on 4,207 participants of the Busselton Health Study (BHS). Heat maps were constructed to visualise the relative differences in lipidomic profile between men and women. Multivariable linear regression analyses, including sex-interaction terms, were performed to assess the associations of lipid species with cardiometabolic phenotypes. Associations with age and sex were found for 472 (66.9%) and 583 (82.6%) lipid species, respectively. We further demonstrated that age-associated lipidomic fingerprints differed by sex. Specific classes of ether-phospholipids and lysophospholipids (calculated as the sum composition of the species within the class) were inversely associated with age in men only. In analyses with women alone, higher triacylglycerol and lower lysoalkylphosphatidylcholine species were observed among postmenopausal women compared with premenopausal women. We also identified sex-specific associations of lipid species with obesity. Lysophospholipids were negatively associated with BMI in both sexes (with a larger effect size in men), whilst acylcarnitine species showed opposing associations based on sex (positive association in women and negative association in men). Finally, by utilising specific lipid ratios as a proxy for enzymatic activity, we identified stearoyl CoA desaturase (SCD-1), fatty acid desaturase 3 (FADS3), and plasmanylethanolamine Δ1-desaturase activities, as well as the sphingolipid metabolic pathway, as constituent perturbations of cardiometabolic phenotypes. Our analyses elucidate the effect of age and sex on lipid metabolism by offering a comprehensive view of the lipidomic profiles associated with common cardiometabolic risk factors. These findings have implications for age- and sex-dependent lipid metabolism in health and disease and suggest the need for sex stratification during lipid biomarker discovery, establishing biological reference intervals for assessment of disease risk.


Assuntos
Envelhecimento/sangue , Lipidômica , Lipídeos/sangue , Obesidade/metabolismo , Caracteres Sexuais , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Metabolismo dos Lipídeos , Masculino , Menopausa/sangue , Pessoa de Meia-Idade , Circunferência da Cintura
3.
Eur Respir J ; 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943407

RESUMO

THE QUESTION ADDRESSED BY THE STUDY: Are long-term Household Air Pollutions (HAPs) associated with asthma and lung function decline in middle-aged adults, and whether these associations were modified by GST gene variants, ventilation and atopy. MATERIALS AND METHODS: Prospective data on HAPs (heating, cooking, mould, smoking) and asthma were collected in the Tasmanian Longitudinal Health Study (TAHS) at mean ages 43 and 53 years (n=3314). Subsamples had data on lung function (n=897) and GST gene polymorphisms (n=928). Latent class analysis was used to characterise longitudinal patterns of exposure. Regression models assessed associations and interactions. RESULTS: We identified seven longitudinal HAP profiles. Of these, 3 were associated with persistent asthma, greater lung function decline and %reversibility by age 53 years, compared to "least exposed" profile, for who used reverse cycle air conditioning, electric cooking and without smoking. "All gas"(OR:2.64, 95%CI 1.22-5.70), "wood heating/smoking" (2.71, 1.21-6.05) and "wood heating/gas cooking" (2.60, 1.11-6.11) were associated with persistent asthma, greater lung function decline and %reversibility. Participants with GSTP1 Ile/Ile genotypes were at a higher risk of asthma or greater lung function decline when exposed compared to other genotypes. Exhaust fan use and opening windows frequently could reduce the adverse effects of HAP produced by combustion heating and cooking on current asthma presumably through increasing ventilation. ANSWER TO THE QUESTION: Exposures to wood heating, gas cooking and heating, and tobacco smoke over 10 years increased the risks of persistent asthma, lung function decline and %reversibility, with evidence of interaction by GST genes and ventilation.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32761187

RESUMO

BACKGROUND: Telomeres are essential DNA-protein complexes whose attrition results in cellular dysfunction and senescence. Leucocyte telomere length (LTL) correlates with tissue telomere length, representing a biomarker for biological age. However its predictive value for mortality risk, and for cardiovascular vs cancer deaths, in older adults remains uncertain. METHODS: We studied 3,608 community-dwelling men aged 77.0±3.6 years. LTL was measured using multiplex quantitative PCR, expressed as amount of telomeric DNA relative to single-copy control gene (T/S ratio). Deaths from any cause, cardiovascular disease (CVD) and cancer were ascertained using data linkage. Curve fitting used restricted cubic splines and Cox regression analyses adjusted for age, cardiometabolic risk factors and prevalent disease. RESULTS: There was a U-shaped association of LTL with all-cause mortality. Men with T/S ratio in the middle quartiles had lower mortality (quartiles, Q2 vs Q1, hazard ratio HR=0.86, 95% confidence interval CI=0.77-0.97, p=0.012, Q3 vs Q1 HR=0.88, CI=0.79-0.99, p=0.032). There was no association of LTL with CVD mortality. There was a U-shaped association of LTL with cancer mortality. Men with LTL in the middle quartiles had lower risk of cancer death (Q2 vs Q1, HR=0.73, CI=0.59-0.90, p=0.004, Q3 vs Q1, HR=0.75, CI=0.61-0.92, p=0.007). CONCLUSIONS: In older men both shorter and longer LTL are associated with all-cause mortality. A similar U-shaped association was seen with cancer deaths, with no association found for cardiovascular deaths. Further research is warranted to explore the prognostic utility of LTL in ageing.

6.
J Allergy Clin Immunol ; 146(5): 1035-1044.e12, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32289338

RESUMO

BACKGROUND: Although the impact of early life acetaminophen on asthma risk is still not clear, potential interactions with glutathione S-transferase (GST) genes due to reduced antioxidant function in particular polymorphisms, and possible impact on lung function, have never been investigated in adolescents. OBJECTIVE: We aimed to investigate associations between early life acetaminophen use and adolescent asthma and lung function and to assess potential interactions by GST polymorphisms. METHODS: Acetaminophen use was recorded 18 times up to age 2 years (n = 575 [92.7%]). Participants were genotyped for GST polymorphisms (GSTM1/T1/P1) (n = 429 [69.2%]). Asthma and lung function were measured at 12 (n = 365 [58.9%]) and 18 years (n = 413 [66.6%]). Regression models assessed associations and interactions. RESULTS: Doubling of days of acetaminophen use was associated with reduced prebronchodilator FEV1/forced vital capacity (ß coefficient, -0.10; 95% CI, -0.19 to -0.01) and midexpiratory flow (-0.09; 95% CI, -0.18 to 0) at 18 years, but this association was not found when restricted for nonrespiratory reasons, suggesting confounding by indication. However, in children with GSTM1 null and GSTT1 present, increasing acetaminophen use for nonrespiratory reasons was associated with reduced FEV1 and midexpiratory flow at 18 years (interaction between GSTM1/T1 and acetaminophen P < .05). Increased acetaminophen use was associated with asthma at 18 years for children with GSTP1 Ile/Ile (odds ratio, 1.66; 95% CI, 1.07 to 2.57), but not other GSTP1 genotypes. CONCLUSIONS: These novel findings need to be investigated for consistency in other studies but suggest that children carrying risk genotypes may be susceptible to respiratory consequences from acetaminophen use.

8.
Eur J Endocrinol ; 182(1): 23-33, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31658437

RESUMO

Objective: Effects of insulin-like growth factor 1 (IGF1) and its binding proteins (IGFBPs) on ageing, and their interaction with sex hormones, remain uncertain. We examined associations of plasma IGF1, IGFBP1, IGFBP3, estradiol and testosterone, with leucocyte telomere length (LTL), a marker of biological age, in 2999 community-dwelling men aged 70-84 years. Methods: Plasma IGF1, IGFBP1 and IGFBP3 measured using immunoassay, sex hormones using mass spectrometry. LTL measured by PCR, expressed as ratio of telomeric to single-copy control gene DNA (T/S ratio). Linear regression models adjusted for age and cardio-metabolic risk factors, median splits defined low/high groups. Results: Mean age was 76.7 ± 3.2 years. IGF1 and IGFBP3 showed age-adjusted correlations with LTL (coefficient 0.59, P = 0.001 and 0.45, P = 0.013 respectively), IGFBP1 did not. In multivariable-adjusted models IGF1 and IGFBP3 (but not IGFBP1) were associated with LTL (T/S ratio 0.015 higher per 1 s.d. increase in IGF1, P = 0.007, and 0.011 per 1 s.d. IGFBP3, P = 0.049). IGF1 and estradiol were independently associated with longer telomeres (T/S ratio 0.012 higher per 1 s.d. increase in estradiol, P = 0.027, when included in model with IGF1). Testosterone was not associated with LTL. Men with both high IGF1 (>133 µg/L) and high estradiol (>70 pmol/L) had longer LTL compared to men with lower values (multivariable-adjusted T/S ratio 1.20 vs 1.16, P = 0.018). Conclusions: Higher IGF1 and IGFBP3 are independently associated with longer telomeres in older men. Additive associations of higher IGF1 and higher estradiol with telomere length are present. Further studies are needed to determine whether these hormonal exposures cooperate to slow biological aging.


Assuntos
Biomarcadores/sangue , Estradiol/sangue , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Leucócitos/metabolismo , Telômero/metabolismo , Idoso , Idoso de 80 Anos ou mais , Humanos , Imunoensaio , Masculino , Fatores de Risco , Testosterona/sangue
9.
Chest ; 157(2): 334-341, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31669428

RESUMO

BACKGROUND: Although there is ongoing debate regarding the impact of early postnatal exposure to antibiotics on the development of asthma, the possibility that antibiotic exposure may impair lung function has not previously been examined. Furthermore, it is unclear if specific types of antibiotics may have a greater effect, or if children with genetic mutations in the oxidative stress response glutathione S-transferase (GST) superfamily may be at greater risk. METHODS: Parent-reported data of childhood antibiotic use from birth to 2 years, including type and indication, were collected from a birth cohort of 620 infants with a family history of allergy. Spirometry was performed at age 12 and 18 years, and results are presented as z scores. Participants were genotyped for GST-P, GST-M, and GST-T polymorphisms. Linear regression models were used to investigate the associations while adjusting for confounding factors. RESULTS: Neither increasing days of exposure nor earlier exposure to antibiotics was associated with reduced FEV1 (at 18 years, per doubling of days of exposure = -0.03 z score units; 95% CI, -0.11 to 0.04) or FVC (< 0.01; 95% CI, -0.08 to 0.07). There was no evidence that GST-risk polymorphisms (M1, P1, and T1) increased susceptibility, and specific types of antibiotics also did not increase risk of lung function deficits. CONCLUSIONS: Increasing exposure to oral antibiotics in early postnatal life was not associated with reduced lung function in children with a family history of allergic diseases. Although unwarranted use of antibiotics in children should be minimized, concerns regarding long-term lung health should not be a driving influence for this rationalization of use.


Assuntos
Antibacterianos/uso terapêutico , Asma/epidemiologia , Volume Expiratório Forçado/fisiologia , Pulmão/fisiopatologia , Capacidade Vital/fisiologia , Adolescente , Asma/genética , Asma/fisiopatologia , Criança , Dermatite Atópica , Família , Feminino , Hipersensibilidade Alimentar , Volume Expiratório Forçado/genética , Interação Gene-Ambiente , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Estudos Longitudinais , Macrolídeos/uso terapêutico , Masculino , Estresse Oxidativo/genética , Penicilinas/uso terapêutico , Polimorfismo Genético , Rinite Alérgica , Fatores de Risco , Sulfonamidas/uso terapêutico , Capacidade Vital/genética
10.
Int J Epidemiol ; 49(2): 467-476, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31670764

RESUMO

The Wittenoom crocidolite (blue asbestos) mine and mill ceased operating in 1966. The impact of this industry on asbestos-related disease in Western Australia has been immense. Use of the employment records of the Australian Blue Asbestos Company and records of the Wittenoom township residents has permitted two cohorts of people with virtually exclusive exposure to crocidolite to be assembled and studied. Follow-up of these two cohorts has been conducted through data linkage with available hospital, mortality and cancer records. The evolution of asbestos-related disease has been recorded and, with the establishment of exposure measurements, quantitative exposure-response relationships have been estimated. There has been an ongoing epidemic of mortality from lung cancer and malignant mesothelioma and, less so, from asbestosis. Wittenoom crocidolite was used extensively in asbestos-cement products in Western Australia. As a result, the state has recorded a higher malignant-mesothelioma mortality rate than in any other Australian state and in any defined general population in the world. Thus, the legacy of Wittenoom has extended beyond the mine and the town, and is still evident more than 50 years after the closure of the mine.

12.
Sci Rep ; 9(1): 9439, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31263163

RESUMO

Type 2 diabetes (T2D) affects the health of millions of people worldwide. The identification of genetic determinants associated with changes in glycemia over time might illuminate biological features that precede the development of T2D. Here we conducted a genome-wide association study of longitudinal fasting glucose changes in up to 13,807 non-diabetic individuals of European descent from nine cohorts. Fasting glucose change over time was defined as the slope of the line defined by multiple fasting glucose measurements obtained over up to 14 years of observation. We tested for associations of genetic variants with inverse-normal transformed fasting glucose change over time adjusting for age at baseline, sex, and principal components of genetic variation. We found no genome-wide significant association (P < 5 × 10-8) with fasting glucose change over time. Seven loci previously associated with T2D, fasting glucose or HbA1c were nominally (P < 0.05) associated with fasting glucose change over time. Limited power influences unambiguous interpretation, but these data suggest that genetic effects on fasting glucose change over time are likely to be small. A public version of the data provides a genomic resource to combine with future studies to evaluate shared genetic links with T2D and other metabolic risk traits.


Assuntos
Glicemia/genética , Grupo com Ancestrais do Continente Europeu/genética , Estudo de Associação Genômica Ampla , Glicemia/análise , Diabetes Mellitus Tipo 2/genética , Feminino , Variação Genética , Genótipo , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único
14.
BMJ Open ; 9(3): e024594, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30867201

RESUMO

INTRODUCTION: The skin is an important barrier against environmental allergens, but infants have relatively impaired skin barrier function. There is evidence that impaired skin barrier function increases the risk of allergic sensitisation, atopic dermatitis (AD) and food allergy. We hypothesise that regular prophylactic use of emollients, particularly those that are designed to improve skin barrier structure and function, will help prevent these conditions. With the aim of determining if application of a ceramide-dominant emollient two times per day reduces the risk of AD and food allergy, we have commenced a multicentre phase III, outcome assessor blinded, randomised controlled trial of this emollient applied from birth to 6 months. METHODS AND ANALYSIS: Infants (n=760) with a family history of allergic disease will be recruited from maternity hospitals in Melbourne. The primary outcomes are as follows: the presence of AD, assessed using the UK Working Party criteria, and food allergy using food challenge, in the first 12 months of life as assessed by a blinded study outcome assessor. Secondary outcomes are as follows: food sensitisation (skin prick test), skin barrier function, AD severity, the presence of new onset AD after treatment cessation (between 6 and 12 months) and the presence of parent reported AD/eczema. Recruitment commenced in March 2018. ETHICS AND DISSEMINATION: The PEBBLES Study is approved by the Human Research Ethics Committees of the Royal Children's Hospital (RCH) (#37090A) and the Mercy Hospital for Women (2018-008). Parents or guardians will provide written informed consent. Outcomes will be disseminated through peer-reviewed publications and presented at scientific conferences. TRIAL REGISTRATION NUMBERS: ACTRN12617001380381 and NCT03667651.


Assuntos
Ceramidas/administração & dosagem , Colesterol/administração & dosagem , Dermatite Atópica/prevenção & controle , Emolientes/administração & dosagem , Ácidos Graxos/administração & dosagem , Hipersensibilidade Alimentar/prevenção & controle , Dermatite Atópica/genética , Combinação de Medicamentos , Hipersensibilidade Alimentar/genética , Humanos , Lactente , Recém-Nascido , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego
15.
Nat Genet ; 51(3): 481-493, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30804560

RESUMO

Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.


Assuntos
Predisposição Genética para Doença/genética , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Fumar/genética
16.
Chest ; 155(1): 94-102, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30616740

RESUMO

BACKGROUND: Glutathione S-transferase (GST) genes are involved in the management of oxidative stress in the lungs. We aimed to determine whether they modify the associations between early life smoke exposure and adverse lung health outcomes. METHODS: The Melbourne Atopy Cohort study (a high-risk birth cohort) enrolled 620 children and followed them prospectively from birth. We recorded perinatal tobacco smoke exposure, asthma, and lung function at 12 (59%) and 18 years (66%) and genotyped for GSTM1, GSTT1, and GSTP1 (69%). RESULTS: GST genotypes were found to interact with tobacco smoke exposure on lung function outcomes (P interaction ≤ .05). Only among children with GSTT1 null genotypes was exposure to mother's, father's, or parental tobacco smoke in early life associated with an increased risk of reductions in prebronchodilator (BD) FEV1 and FVC at both 12 and 18 years. These associations were not seen in children with GSTT1 present. Similarly, only among children with GSTM1 null genotypes was exposure to father's or parental smoking associated with reductions in pre- and post-BD FEV1 and FVC at 18 years. Only among children with Ile/Ile genotypes of GSTP1 was exposure to mother's smoking associated with increased risk of reduced FEV1 at 18 years, but this was not the case among children with Val/Val or Ile/Val genotypes. CONCLUSIONS: Our study provides evidence of interaction between early tobacco smoke exposure and GST genotypes on lung function. Carriers of GST null mutations and GSTP1 Ile/Ile alleles may be more susceptible when exposed to tobacco smoke in early life. These findings support stronger recommendations to protect all infants from tobacco smoke exposure. TRIAL REGISTRY: Australian and New Zealand Clinical Trials Registry; No.: ACTRN12609000734268; URL: http://www.anzctr.org.au/.


Assuntos
Asma/fisiopatologia , Previsões , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Polimorfismo Genético , Poluição por Fumaça de Tabaco/efeitos adversos , Adolescente , Asma/genética , Asma/metabolismo , Criança , DNA/genética , Feminino , Seguimentos , Fluxo Expiratório Forçado/fisiologia , Predisposição Genética para Doença , Genótipo , Glutationa S-Transferase pi/metabolismo , Glutationa Transferase/metabolismo , Humanos , Pulmão/fisiopatologia , Masculino , Estudos Retrospectivos , Fatores de Risco
17.
Clin Endocrinol (Oxf) ; 90(2): 301-311, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30353958

RESUMO

CONTEXT: Pituitary luteinizing hormone (LH) stimulates testicular production of testosterone (T) which is metabolized to dihydrotestosterone (DHT) by 5α-reductase and to oestradiol (E2) by aromatase. How the activity of population variants in these enzymes impacts on gonadal function is unclear. We examined whether polymorphisms in 5α-reductase (SRD5A2) and aromatase (CYP19A1) genes predict circulating sex hormone concentrations. DESIGN: Cross-sectional analysis of 1865 community-dwelling men aged 50.4 ± 16.8 years. MEASUREMENTS: Early morning sera assayed for T, DHT and E2 (mass spectrometry), and SHBG and LH (immunoassay). Two SRD5A2 and eleven CYP19A1 polymorphisms were analysed by PCR. Regression models were adjusted for age and cardiometabolic risk factors. RESULTS: SRD5A2 polymorphism rs9282858 GA vs. GG was associated with higher serum T (+1.5 nmol/L, P < 0.001) and higher SHBG (+3.3 nmol/L, P = 0.001). CYP19A1 polymorphisms were associated with higher serum E2 and lower LH in reciprocal fashion, from which the two-copy haplotype rs10046 = T/rs2899470 = G/rs11575899 = I/rs700518 = G/rs17703883 = T was associated with higher E2 (63.4 vs. 56.5 pmol/L, P = 0.001) and lower LH (3.9 vs. 4.5 IU/L, P = 0.001) compared to null copies. Conversely, rs10046 = C/rs2899470 = T/rs11575899 = D/rs700518 = A/rs17703883 = C was associated with lower E2 (51.8 vs. 62.0 pmol/L, P = 0.001) and higher LH (5.7 vs. 3.9 IU/L, P < 0.001). These haplotypes were associated primarily with differences in E2 in men <65 years and LH in men ≥65 years. CONCLUSIONS: A 5α-reductase polymorphism predicts circulating T and SHBG, while aromatase polymorphisms predict E2 and LH in reciprocal fashion. Age and aromatase polymorphisms interact to affect E2 and LH. How these functional polymorphisms impact on male reproductive and general health outcomes requires further study.


Assuntos
Aromatase/genética , Colestenona 5 alfa-Redutase/genética , Estradiol/sangue , Hormônio Luteinizante/sangue , Polimorfismo de Nucleotídeo Único , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue , Adulto , Fatores Etários , Idoso , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade
18.
Immunobiology ; 224(1): 110-115, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30446335

RESUMO

BACKGROUND: Increased body fat may be associated with an increased risk of developing an underlying pro-inflammatory state, thus leading to greater risk of developing certain chronic conditions. Immunoglobulin G has the ability to exert both anti- and pro-inflammatory effects, and the N-glycosylation of the fragment crystallisable portion is involved in mediating this process. Body mass index, a rudimentary yet gold standard indication for body fat, has been shown to be associated with agalactosylated immunoglobulin G N-glycans. AIM: We aimed to determine the association between increased body fat and the immunoglobulin G glycosylation features, comparing body mass index to other measures of body fat distribution. METHODS: We investigated a sample of 637 community-based 45-69 year olds, with mixed phenotypes, residing in Busselton, Western Australia. Body mass index and the waist-to-hip and waist-to-height ratios were calculated using anthropometry, while dual-energy x-ray absorptiometry was performed to gain an accurate measure of total and area specific body fat. Serum immunoglobulin GN-glycans were analysed by ultra-performance liquid chromatography. RESULTS: Twenty-two N-glycan peaks were found to be associated with at least one of the fat measures. While the previous association of body mass index to agalactosylated immunoglobulin G was replicated, measures of central adiposity explained the most variation in the immunoglobulin G glycome. CONCLUSION: Central adiposity is associated with an increased pro-inflammatory fraction of immunoglobulin G, suggesting that the android/gynoid ratio or waist-to-height ratio instead be considered when controlling for adiposity in immunoglobulin G glycome biomarker studies.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Adiposidade/fisiologia , Imunoglobulina G/química , Mediadores da Inflamação/química , Obesidade/epidemiologia , Absorciometria de Fóton , Idoso , Antropometria , Austrália/epidemiologia , Índice de Massa Corporal , Cromatografia Líquida , Pesquisa Participativa Baseada na Comunidade , Feminino , Glicosilação , Humanos , Imunoglobulina G/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Risco
19.
Clin Exp Allergy ; 49(3): 331-340, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30288821

RESUMO

BACKGROUND: Markers of microbial exposure are thought to be associated with risk of allergic sensitization; however, the associations are inconsistent and may be related to gene-environment interactions. OBJECTIVE: To examine the relationship between polymorphisms in the CD14 gene and allergic sensitization and whether sibling exposure, as a marker of microbial exposure, modified this relationship. METHODS: We used data from the Tasmanian Longitudinal Health Study and the Melbourne Atopy Cohort Study. Two CD14 polymorphisms were genotyped. Allergic sensitization was defined by a positive response to a skin prick test. Sibling exposure was measured as cumulative exposure to siblings before age 6 months, 2 and 4 years. Logistic regression and multi-level mixed-effects logistic regression were used to examine the associations. Effect estimates across the cohorts were pooled using random-effects meta-analysis. RESULTS: CD14 SNPs were not individually associated with allergic sensitization in either cohort. In TAHS, cumulative sibling exposure before age 6 months, 2 and 4 years was each associated with a reduced risk of allergic sensitization at age 45 years. A similar effect was observed in MACS. Meta-analysis across the two cohorts showed consistent evidence of an interaction between cumulative sibling exposure before 6 months and the rs5744455-SNP (P = 0.001) but not with the rs2569190-SNP (P = 0.60). The pooled meta-analysis showed that the odds of sensitization with increasing cumulative exposure to sibling before 6 months of age was 20.9% smaller in those with the rs5744455-C-allele than the T-allele (OR = 0.83 vs 1.05, respectively). CONCLUSION AND CLINICAL RELEVANCE: Cumulative sibling exposure reduced the risk of sensitization from childhood to middle age in genetically susceptible individuals.


Assuntos
Asma , Exposição Ambiental/efeitos adversos , Receptores de Lipopolissacarídeos , Polimorfismo de Nucleotídeo Único , Irmãos , Adolescente , Alelos , Asma/epidemiologia , Asma/genética , Asma/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Receptores de Lipopolissacarídeos/genética , Receptores de Lipopolissacarídeos/imunologia , Estudos Longitudinais , Masculino , Metanálise como Assunto , Estudos Prospectivos , Tasmânia/epidemiologia
20.
Clin Endocrinol (Oxf) ; 90(4): 562-569, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30561819

RESUMO

CONTEXT: Telomeres protect chromosomes from damage, and shorter leucocyte telomere length (LTL) is a marker of advancing biological age. The association between testosterone (T) and its bioactive metabolites, dihydrotestosterone (DHT) and oestradiol (E2) with telomere length, particularly in older men, is uncertain. The study aimed to clarify associations of sex hormones with LTL in older men. PARTICIPANTS AND METHODS: We used cross-sectional data from 2913 men aged 76.7 ± 3.2 years with morning blood samples assayed for T, DHT, E2 (mass spectrometry), and sex hormone-binding globulin (SHBG, immunoassay), to correlate sex hormones with LTL measured using PCR and expressed as T/S ratio in multivariable linear regression models adjusted for age, cardiometabolic risk factors and cardiovascular disease history. RESULTS: Average difference per decade of age was T -0.46 nmol/L, DHT -0.11 nmol/L, E2 -7.5 pmol/L, SHBG +10.2 nmol/L and LTL (T/S ratio) -0.065. E2 correlated with T/S ratio (r = 0.038, P = 0.039) and SHBG was inversely correlated (r = -0.053, P = 0.004). After multivariable adjustment, E2 was associated with T/S ratio (per 1 SD increase E2: coefficient 0.011, P = 0.043), T and DHT were not associated. When E2 and SHBG were simultaneously included, E2 remained positively (coefficient 0.014, P = 0.014) and SHBG inversely (coefficient -0.013, P = 0.037) associated with T/S ratio. CONCLUSIONS: In older men, neither T nor DHT is associated with LTL while E2 is independently associated with LTL and SHBG is inversely associated, thus relating sex hormone exposure to lower biological age. Further research is needed to determine causality and clarify the role of sex hormones in male ageing.


Assuntos
Hormônios Esteroides Gonadais/sangue , Telômero/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Envelhecimento/fisiologia , Estudos Transversais , Di-Hidrotestosterona/sangue , Estradiol/sangue , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Testosterona/sangue , Adulto Jovem
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