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2.
Am J Hum Genet ; 105(1): 15-28, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31178129

RESUMO

Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 × 10-7). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r2 > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 × 10-4) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.

3.
Am J Hum Biol ; 31(3): e23237, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30950564

RESUMO

OBJECTIVE: Cardiovascular disease (CVD) is rising in low and middle-income countries, but studies of CVD epidemiology in such settings often focus on risk factors rather than measures of disease progression. Here we use the ankle brachial index (ABI) to assess the prevalence of peripheral artery disease (PAD) among older women living in Metropolitan Cebu, Philippines, and relationships between ABI and CVD risk factors and body composition. METHODS: ABI was measured using the Doppler technique in 538 female participants in the 2015 Cebu Longitudinal Health and Nutrition Survey (mean age 58 years, range 47-78 years). ABI was related to a panel of CVD risk factors measured in 2005 and 2012, and to 2012 body composition measures. RESULTS: The prevalence of PAD (1.8%) was among the lowest reported in any comparably-aged sample, and only 9.9% of participants had an ABI indicating borderline PAD risk. Smoking (P < 0.011) and use of CVD medications (P < 0.0001) predicted lower ABI (indicating higher PAD risk), which was also lower in relation to 2012 systolic blood pressure (P < 0.054). ABI was unrelated to other CVD risk factors. An apparent protective relationship between body mass index (BMI) and ABI, noted in previous studies, was found to be confounded by protective relationships between ABI and fat free mass, height, and grip strength (all P < 0.05). CONCLUSIONS: The prevalence of PAD is low in Cebu Longitudinal Health and Nutrition Survey participants, and ABI was related to few CVD risk factors. Past reports of lower PAD risk in relation to BMI may reflect confounding by lean mass, which has protective relationships with ABI.

4.
Am J Hum Biol ; 31(3): e23245, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30980448

RESUMO

OBJECTIVES: The maternal environment during gestation influences offspring health at birth and throughout the life course. Recent research has demonstrated that endogenous immune processes such as dysregulated inflammation adversely impact birth outcomes, increasing the risk for preterm birth and restricted fetal growth. Prior analyses examining this association suggest a relationship between maternal C-reactive protein (CRP), a summary measure of inflammation, and offspring anthropometric outcomes. This study investigates pro- and anti-inflammatory cytokines, and their ratio, to gain deeper insight into the regulation of inflammation during pregnancy. METHODS: IL6, IL10, TNFɑ, and CRP were quantified in dried blood spots collected in the early third trimester (mean = 29.9 weeks) of 407 pregnancies in Metropolitan Cebu, Philippines. Relationships between these immune markers and offspring anthropometrics (birth weight, length, head circumference, and sum of skinfold thicknesses) were evaluated using multivariate regression analyses. Ratios of pro- to anti-inflammatory cytokines were generated. RESULTS: Higher maternal IL6 relative to IL10 was associated with reduced offspring weight and length at birth. Individual cytokines did not predict birth outcomes. CONCLUSIONS: Consistent with the idea that the relative balance of cytokines with pro- and anti-inflammatory effects is a key regulator of inflammation in pregnancy, the IL6:IL10 ratio, but neither cytokine on its own, predicted offspring birth outcomes. Our findings suggest that prior reports of association between CRP and fetal growth may reflect, in part, the balance between pro- and anti-inflammatory cytokines, and that the gestational environment is significantly shaped by cytokine imbalance.

5.
Geriatrics (Basel) ; 3(4)2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30450359

RESUMO

As life expectancy and obesity increase in low and middle-income countries, the relationship of weight status to functional outcomes in older adults in these settings requires attention. We examined how overweight (BMI > 25 kg/m2), obesity (BMI > 30 kg/m2), and high waist circumference (WC > 80 cm) related to grip strength, timed up-and-go, and development of limitations in mobility, activities of daily living (ADL), and instrumental activities of daily living (IADL) among Filipino women. We analyzed data from seven rounds of the Cebu Longitudinal Health and Nutrition Survey (1994, n = 2279 to 2015, n = 1568, age 49-78 years) to examine how women's reports of functional limitations related to their prior WC, and how their grip strength and timed up-and-go related to concurrently measured overweight and obesity, adjusted for age, socioeconomic status, and urbanicity. High WC was associated with higher odds of subsequent mobility and IADL limitations. Chronic disease morbidity (sum of self-reported arthritis, high blood pressure, heart disease, diabetes, and cancer) fully mediated the association of high WC with ADL and IADL limitations, but not physical/mobility limitations. Longer up-and-go times, and higher grip strength were related to overweight and obesity. Results emphasize the need for obesity prevention to reduce chronic diseases and maintain good functional status as women age.

6.
Asia Pac J Public Health ; 30(6): 561-571, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30221978

RESUMO

Obesity, hypertension, and diabetes have risen dramatically in Asia, but few cohort studies track age and secular trends in these conditions. We use Cebu (The Philippines) Longitudinal Health and Nutrition survey data to document 1998 to 2015 prevalence and co-occurrence of body mass index (BMI; >25 kg/m2), high waist circumference (WC; >80 cm), elevated blood pressure (EBP; systolic ⩾130 or diastolic ⩾85 mm Hg), and type 2 diabetes among ~2000 women aged 29 to 62 years in 1998; and identify their relationship to community, household, and individual factors using longitudinal logistic regression. Prevalence (1998-2015) rates were 35% to 49%, BMI >25 kg/m2; 32% to 58% high WC; 21% to 59% EBP; and 2% to 14% diabetes. Only 20% of women had none of these conditions in 2015. Diabetes was strongly driven by age and secular trends in high WC related to higher socioeconomic status and urbanization. Hypertension increased with age in lower socioeconomic status rural and more affluent urban women. Results underscore the continuing need for public health measures to prevent obesity and to identify and treat hypertension and diabetes.

7.
Am J Hum Biol ; 29(6)2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28759132

RESUMO

OBJECTIVES: The ratio of the length of the second to the fourth digit (2D:4D) of the hand is often used as an index of prenatal androgen exposure but it might also be affected by androgens during "minipuberty," a period of temporarily high testosterone (T) production in the first few months of life. To examine this, we tested the prediction that men with lower 2D:4D ratios had greater weight growth velocities during the first months of life-a metric recently shown to correlate with concurrent T levels. METHODS: We related early growth data to 2D:4D ratios of both hands measured in 756 men (25-26 years) from Cebu, The Philippines. RESULTS: Birth-to-fourth-month (B4M) weight gain velocity (a proxy of early postnatal androgen action) was not associated with adult 2D:4D ratios of either hand, when the latter was measured continuously. When comparing men with more male-typical digit ratios (<1.0) to those with more female-typical ratios (≥ 1.0), the group of men with more male-typical ratios had greater B4M weight velocity, but this was only the case for the left hand. CONCLUSIONS: We found modest evidence that adult digit ratios relate to an anthropometric correlate of androgen exposure during minipuberty. Definitive assessment of the role of postnatal T in shaping digit ratios will require direct measures of perinatal T related to longitudinally assessed digit ratios.


Assuntos
Androgênios/metabolismo , Dedos/anatomia & histologia , Crescimento , Adulto , Antropometria , Dedos/crescimento & desenvolvimento , Humanos , Lactente , Recém-Nascido , Masculino , Filipinas
8.
Proc Natl Acad Sci U S A ; 114(29): 7611-7616, 2017 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-28673994

RESUMO

Chronic inflammation contributes to a wide range of human diseases, and environments in infancy and childhood are important determinants of inflammatory phenotypes. The underlying biological mechanisms connecting early environments with the regulation of inflammation in adulthood are not known, but epigenetic processes are plausible candidates. We tested the hypothesis that patterns of DNA methylation (DNAm) in inflammatory genes in young adulthood would be predicted by early life nutritional, microbial, and psychosocial exposures previously associated with levels of inflammation. Data come from a population-based longitudinal birth cohort study in metropolitan Cebu, the Philippines, and DNAm was characterized in whole blood samples from 494 participants (age 20-22 y). Analyses focused on probes in 114 target genes involved in the regulation of inflammation, and we identified 10 sites across nine genes where the level of DNAm was significantly predicted by the following variables: household socioeconomic status in childhood, extended absence of a parent in childhood, exposure to animal feces in infancy, birth in the dry season, or duration of exclusive breastfeeding. To evaluate the biological significance of these sites, we tested for associations with a panel of inflammatory biomarkers measured in plasma obtained at the same age as DNAm assessment. Three sites predicted elevated inflammation, and one site predicted lower inflammation, consistent with the interpretation that levels of DNAm at these sites are functionally relevant. This pattern of results points toward DNAm as a potentially important biological mechanism through which developmental environments shape inflammatory phenotypes across the life course.


Assuntos
Metilação de DNA , Meio Ambiente , Inflamação/genética , Meio Social , Biomarcadores , Aleitamento Materno , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/genética , Pré-Escolar , Estudos de Coortes , Epigênese Genética , Feminino , Perfilação da Expressão Gênica , Genoma , Inquéritos Epidemiológicos , Humanos , Sistema Imunitário , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Filipinas , Fatores de Risco , Classe Social , Adulto Jovem
9.
PLoS One ; 12(2): e0171299, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28158229

RESUMO

BACKGROUND: The effectiveness of prenatal care for improving birth and subsequent child outcomes in low-income countries remains controversial, with much of the evidence to date coming from high-income countries and focused on early-life outcomes. We examined associations between prenatal care visits and birth weight, height-for-age at 24 months and attained schooling in four low- and middle-income countries. METHODS: We pooled data from prospective birth-cohort studies from Brazil, Guatemala, Philippines and South Africa. We created a prenatal care utilization index based on the number and timing of prenatal visits. Associations were examined between this index and birth weight, height-for-age at 24 months, and highest attained schooling grade until adulthood. RESULTS: Among 7203 individuals in the analysis, 68.9% (Philippines) to 96.7% (South Africa) had at least one prenatal care visit, with most having at least four visits. Over 40% of Brazilians and Guatemalans had their first prenatal visit in the first trimester, but fewer Filipinos (13.9%) and South Africans (19.8%) did so. Prenatal care utilization was not significantly associated with birth weight (p>0.05 in pooled data). Each unit increase in the prenatal care utilization index was associated with 0.09 (95% CI 0.04 to 0.15) higher height-for-age z-score at 24 months and with 0.26 (95% CI 0.17 to 0.35) higher schooling grades attained. Although there was some heterogeneity and greater imprecision across sites, the results were qualitatively similar among the four different populations. CONCLUSIONS: While not related to birth weight, prenatal care utilization was associated with important outcomes later in life, specifically higher height-for-age at 24 months and higher attained school grades. These results suggest the relevance of prenatal care visits for human capital outcomes important over the lifecycle.


Assuntos
Desenvolvimento Infantil , Países em Desenvolvimento/estatística & dados numéricos , Educação/estatística & dados numéricos , Cuidado Pré-Natal/estatística & dados numéricos , Instituições Acadêmicas , Criança , Feminino , Humanos , Renda , Masculino , Aceitação pelo Paciente de Cuidados de Saúde , Gravidez
10.
Am J Hum Biol ; 29(4)2017 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-28121388

RESUMO

OBJECTIVES: Telomeres are repetitive DNA at chromosomes ends that shorten with age due to cellular replication and oxidative stress. As telomeres shorten, this can eventually place limits on cell replication and contribute to senescence. Infections are common during early development and activate cellular immune responses that involve clonal expansion and oxidative stress. As such, a high infectious disease burden might shorten blood telomere length (BTL) and accelerate the pace of immune senescence. METHODS: To test this, BTL measured in young adults (21.7 ± 0.3 years old) from the Philippines (N = 1,759) were linked to prospectively collected early life data on infectious burden. RESULTS: As predicted, increased early life diarrheal prevalence was associated with shorter adult BTL. The association was most marked for infections experienced from 6 to 12 months, which corresponds with weaning and maximal diarrheal burden. A standard deviation increase in infections at 6-12 m predicts a 45 bp decrease in BTL, equivalent to 3.3 years of adult telomeric aging in this population. Contrary to expectations, breastfeeding duration was not associated with BTL, nor did effects vary by sex. CONCLUSIONS: These findings show that infancy diarrheal disease predicts a marker of cellular aging in adult immune cells. These findings suggest that early life infectious burden may influence late life health, or alternatively, that short TL in early life increases infectious disease susceptibility.


Assuntos
Sangue/metabolismo , Aleitamento Materno , Diarreia/epidemiologia , Homeostase do Telômero , Encurtamento do Telômero , Aleitamento Materno/estatística & dados numéricos , Feminino , Humanos , Masculino , Morbidade , Filipinas/epidemiologia , Estudos Prospectivos , Fatores de Tempo , Adulto Jovem
11.
Eur J Nutr ; 56(1): 295-308, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26497538

RESUMO

PURPOSE: Telomeres, DNA-protein structures that cap and protect chromosomes, are thought to shorten more rapidly when exposed to chronic inflammation and oxidative stress. Diet and nutritional status may be a source of inflammation and oxidative stress. However, relationships between telomere length (TL) and diet or adiposity have primarily been studied cross-sectionally among older, overweight/obese populations and yielded inconsistent results. Little is known about the relationship between diet or body composition and TL among younger, low- to normal-weight populations. It also remains unclear how cumulative exposure to a specific diet or body composition during the years of growth and development, when telomere attrition is most rapid, may be related to TL in adulthood. METHODS: In a sample of 1459 young adult Filipinos, we assessed the relationship between blood TL at ages 20.8-22.5 and measures of BMI z-score, waist circumference, and diet collected between the ages of 8.5 and 22.5. TL was measured using monochrome multiplex quantitative PCR, and diet was measured using multiple 24-h recalls. RESULTS: We found no associations between blood TL and any of the measures of adiposity or between blood TL and the seven dietary factors examined: processed meats, fried/grilled meats and fish, non-fried fish, coconut oil, fruits and vegetables, bread and bread products, and sugar-sweetened beverages. CONCLUSIONS: Considering the inconsistencies in the literature and our null results, small differences in body composition and consumption of any single pro- or anti-inflammatory dietary component may not by themselves have a meaningful impact on telomere integrity, or the impact may differ across distinct ecological circumstances.


Assuntos
Adiposidade/genética , Dieta , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Telômero/ultraestrutura , Magreza/epidemiologia , Composição Corporal , Índice de Massa Corporal , Doença Crônica , Estudos Transversais , Feminino , Seguimentos , Humanos , Inflamação/sangue , Inflamação/genética , Estudos Longitudinais , Masculino , Inquéritos Nutricionais , Estado Nutricional , Obesidade/sangue , Obesidade/genética , Sobrepeso/sangue , Sobrepeso/genética , Filipinas , População Rural , Magreza/sangue , Magreza/genética , População Urbana , Circunferência da Cintura , Adulto Jovem
12.
Res Aging ; 39(2): 275-299, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26475652

RESUMO

The health implications of multigenerational coresidence for older adults is a well-researched topic in the aging literature. Much less is known of its impact for women in midlife. We used data from the Cebu Longitudinal Health and Nutrition Study (2002, 2005, 2007, and 2012) to study the influence of transitions in multigenerational household composition on depressive symptoms for women in midlife transitioning into old age. Our initial analysis showed little effect when we use the conventional classification of nuclear versus extended family and transition in and out of extended family. When we described shifts in the family environment by compositional changes, that is, change in the presence and absence of particular family members, we found significant association between depressive symptoms and two types of role transitions: the loss of a spouse in the household and the entry and exit of grandchildren in the household.

13.
Econ Hum Biol ; 22: 65-81, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27026217

RESUMO

We examine effects of protein and energy intakes on height and weight growth for children between 6 and 24 months old in Guatemala and the Philippines. Using instrumental variables to control for endogeneity and estimating multiple specifications, we find that protein intake plays an important and positive role in height and weight growth in the 6-24 month period. Energy from other macronutrients, however, does not have a robust relation with these two anthropometric measures. Our estimates indicate that in contexts with substantial child undernutrition, increases in protein-rich food intake in the first 24 months can have important growth effects, which previous studies indicate are related significantly to a range of outcomes over the life cycle.


Assuntos
Estatura , Peso Corporal , Proteínas na Dieta , Ingestão de Energia , Transtornos da Nutrição do Lactente/epidemiologia , Aleitamento Materno/estatística & dados numéricos , Diarreia/epidemiologia , Feminino , Guatemala/epidemiologia , Humanos , Lactente , Masculino , Filipinas/epidemiologia , Fatores de Tempo
14.
J Nutr ; 146(2): 353-7, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26764318

RESUMO

BACKGROUND: Rates of overweight and obesity are on the rise globally, and excess adipose tissue may contribute to elevations in inflammation during pregnancy, leading to pregnancy complications and adverse birth outcomes. OBJECTIVE: The purpose of this study was to evaluate adiposity and inflammation in young women as predictors of inflammation in the third trimester of pregnancy in a community-based sample of healthy women. METHODS: Female participants (24-30 y) in a prospective observational cohort study (Cebu Longitudinal Health and Nutrition Survey) were contacted between 2009 and 2014 to identify new pregnancies. A total of 309 women provided data from 409 pregnancies. An in-home interview was scheduled for the third trimester to collect pregnancy information, anthropometric measurements, and a blood sample. Circulating C-reactive protein (CRP) was measured with a high-sensitivity immunoassay. Data collected from assessments in 2005 and 2009 were used to assess body mass index (BMI) and CRP in young adulthood, before pregnancy. Robust regression models were implemented to evaluate BMI and CRP in young adulthood as predictors of pregnancy CRP. RESULTS: Pre-pregnancy BMI was a stronger predictor of third-trimester circulating CRP than BMI in the third trimester. No association was found between pregnancy weight gain and CRP. Pre-pregnancy CRP was a significant predictor of CRP in pregnancy, independent of BMI. CONCLUSIONS: Levels of overweight/obesity and inflammation in young adulthood, before pregnancy, are important predictors of inflammation in the third trimester of pregnancy. These results may have implications for addressing the growing concern about the contribution of obesity to adverse birth outcomes, and they suggest that factors that influence the regulation of inflammation, before pregnancy and independent of adiposity, may be important in shaping the inflammatory response to pregnancy.


Assuntos
Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Inflamação , Obesidade/complicações , Complicações na Gravidez , Terceiro Trimestre da Gravidez , Ganho de Peso , Adiposidade , Adulto , Estudos de Coortes , Feminino , Humanos , Inflamação/sangue , Obesidade/sangue , Sobrepeso , Filipinas , Gravidez , Complicações na Gravidez/sangue , Resultado da Gravidez , Estudos Prospectivos , Adulto Jovem
15.
Vaccine ; 33(17): 2004-8, 2015 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-25795257

RESUMO

BACKGROUND: C-reactive protein (CRP) is increasingly measured as a marker of systemic inflammation that predicts elevated risk for cardiovascular disease. Influenza vaccination is a mild pro-inflammatory stimulus, and the CRP response to vaccination may provide additional information on individual differences in inflammatory response and risk for disease. AIM: To document the pattern of CRP response to influenza vaccination among a large sample of older women in the Philippines. The Philippines exemplifies current global trends toward increasing rates of overweight/obesity, but also maintains relatively high rates of infectious disease. The secondary aim of the study is to investigate the impact of infectious symptoms on the pattern of response to vaccination. METHODS: A community-based sample of 934 women (mean age=55.4 years) received the influenza vaccine. CRP was assessed at baseline and 72h post-vaccination. Descriptive, non-parametric, and parametric analyses were implemented to assess the magnitude of CRP response, and to investigate whether responses were associated with baseline CRP or the presence of infectious symptoms prior to vaccination. RESULTS: Influenza vaccination resulted in a statistically significant CRP response of 0.35mg/L (p<0.001), representing a 30.2% increase from baseline. For individuals with symptoms of infectious disease at baseline, the CRP response was smaller (12.9%) and not statistically significant (p=0.77). Lower CRP at baseline was associated with larger CRP response to vaccination in the entire sample, and among participants without recent symptoms of infection. CONCLUSIONS: Influenza vaccination produces a mild CRP response in the Philippines. This study extends prior research in US and European populations validating influenza vaccination as an in vivo model for investigating the dynamics of inflammation, but also raises potential complications in settings where rates of infectious disease are elevated.


Assuntos
Biomarcadores/análise , Proteína C-Reativa/análise , Inflamação , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Idoso , Feminino , Humanos , Vacinas contra Influenza/administração & dosagem , Pessoa de Meia-Idade , Filipinas , Vacinação
16.
J Hum Lact ; 31(2): 273-81, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25348673

RESUMO

BACKGROUND: Human milk contains many metabolic hormones that may influence infant growth. Milk leptin is positively associated with maternal adiposity and inversely associated with infant growth. Most research has been conducted in populations with higher leptin levels; it is not well understood how milk leptin may vary in lean populations or the associations that reduced leptin may have with infant size for age. It is also largely unknown if associations between maternal body composition and milk leptin persist past 1 year of age. OBJECTIVES: We investigated the association between maternal body composition and milk leptin content in a sample of lean Filipino women and the association between milk leptin content and infant size for age. METHODS: Milk samples were collected at in-home visits from 113 mothers from Cebu, Philippines. Milk leptin content was measured using EIA techniques; anthropometric data, dietary recalls, and household information were also collected. RESULTS: Mean ± standard deviation (SD) milk leptin in this sample was 300.7 ± 293.6 pg/mL, among the lowest previously reported. Mean ± SD maternal percentage body fat was 24.8% ± 3.5%. Mean ± SD infant age was 9.9 ± 7.0 months, and mean ± SD weight for age z-score was -0.98 ± 1.06. Maternal percentage body fat was a significant, positive predictor of milk leptin content. Milk leptin was a significant, inverse predictor of infant weight and body mass index z-scores in infants 1 year old or younger. CONCLUSION: The association between maternal body composition, milk leptin, and infant growth persists in mothers with lean body composition. Milk leptin is not associated with growth in older infants.


Assuntos
Composição Corporal/fisiologia , Aleitamento Materno , Leptina/metabolismo , Leite Humano/metabolismo , Adulto , Grupo com Ancestrais do Continente Asiático , Peso ao Nascer , Desenvolvimento Infantil , Ingestão de Energia , Feminino , Humanos , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Filipinas/epidemiologia , Gravidez , Adulto Jovem
17.
Hum Mol Genet ; 23(4): 1108-19, 2014 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-24105470

RESUMO

Blood levels of adiponectin, an adipocyte-secreted protein correlated with metabolic and cardiovascular risks, are highly heritable. Genome-wide association (GWA) studies for adiponectin levels have identified 14 loci harboring variants associated with blood levels of adiponectin. To identify novel adiponectin-associated loci, particularly those of importance in East Asians, we conducted a meta-analysis of GWA studies for adiponectin in 7827 individuals, followed by two stages of replications in 4298 and 5954 additional individuals. We identified a novel adiponectin-associated locus on chromosome 10 near WDR11-FGFR2 (P = 3.0 × 10(-14)) and provided suggestive evidence for a locus on chromosome 12 near OR8S1-LALBA (P = 1.2 × 10(-7)). Of the adiponectin-associated loci previously described, we confirmed the association at CDH13 (P = 6.8 × 10(-165)), ADIPOQ (P = 1.8 × 10(-22)), PEPD (P = 3.6 × 10(-12)), CMIP (P = 2.1 × 10(-10)), ZNF664 (P = 2.3 × 10(-7)) and GPR109A (P = 7.4 × 10(-6)). Conditional analysis at ADIPOQ revealed a second signal with suggestive evidence of association only after conditioning on the lead SNP (Pinitial = 0.020; Pconditional = 7.0 × 10(-7)). We further confirmed the independence of two pairs of closely located loci (<2 Mb) on chromosome 16 at CMIP and CDH13, and on chromosome 12 at GPR109A and ZNF664. In addition, the newly identified signal near WDR11-FGFR2 exhibited evidence of association with triglycerides (P = 3.3 × 10(-4)), high density lipoprotein cholesterol (HDL-C, P = 4.9 × 10(-4)) and body mass index (BMI)-adjusted waist-hip ratio (P = 9.8 × 10(-3)). These findings improve our knowledge of the genetic basis of adiponectin variation, demonstrate the shared allelic architecture for adiponectin with lipids and central obesity and motivate further studies of underlying mechanisms.


Assuntos
Adiponectina/sangue , Doenças Cardiovasculares/genética , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Grupo com Ancestrais do Continente Asiático , Doenças Cardiovasculares/sangue , Estudos de Coortes , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único
18.
Brain Behav Immun ; 31: 23-30, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22960631

RESUMO

Chronic inflammation is a potentially important pathway through which psychosocial stressors increase risk for cardiovascular disease. However, prior research on stress and inflammation has been conducted almost exclusively in high income, industrialized populations with low levels of infectious disease. In this study we test the hypothesis that psychosocial stressors are associated with elevated concentrations of C-reactive protein (CRP) among young adults in the Philippines (n=1622), who have grown up in an ecological and epidemiological setting that differs substantially from that of the US. In addition, we apply a developmental, ecological perspective to consider whether microbial and nutritional environments in infancy alter patterns of association between stressors and CRP. Data come from the Cebu Longitudinal Health and Nutrition Survey, a prospective cohort study that began collecting data in 1983-1984 when participants were in utero. A series of regression models indicate trends toward significant interactions between perceived stress and environmental factors in infancy, including exposure to animal feces, season of birth, and birth weight. Parental absence in childhood was a significant predictor of CRP in adulthood in interaction with exposure to animal feces in infancy. Positive associations between stressors and CRP were only evident for individuals with lower levels of microbial exposure in infancy, or lower birth weight. These results suggest that early environments influence the development of inflammatory phenotypes in ways that moderate sensitivity to psychosocial stressors in adulthood, and they underscore the value of a comparative, developmental approach to research on social environments, inflammation, and disease.


Assuntos
Proteína C-Reativa/metabolismo , Imunidade Inata/imunologia , Inflamação/complicações , Meio Social , Estresse Psicológico/complicações , Adaptação Psicológica , Adulto , Peso ao Nascer , Estudos de Coortes , Feminino , Inquéritos Epidemiológicos , Humanos , Lactente , Inflamação/sangue , Inflamação/imunologia , Masculino , Privação Materna , Filipinas , Estudos Prospectivos , Estresse Psicológico/sangue , Estresse Psicológico/imunologia , Inquéritos e Questionários
19.
Evol Med Public Health ; 2013(1): 18-23, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24481182

RESUMO

Depression is positively associated with chronic inflammation in industrialized settings with low burdens of infectious disease, but the pattern of association in environments with higher levels of microbial exposure is not known. We measured C-reactive protein (CRP) and interleukin 6 (IL6) in community-based samples of young adults (20-22 years) and older women (35-69 years) in the Philippines. Concentrations of CRP and IL6 were low, and bivariate and multivariate regression analyses indicated no associations between depressive symptoms and inflammation in either sample. Results are interpreted in light of prior research indicating that higher levels of microbial exposure in infancy have lasting effects on the regulation of inflammation, and may prevent the emergence of a relationship between depression and inflammation in adulthood.

20.
Malays J Nutr ; 19(1): 1-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24800380

RESUMO

INTRODUCTION: The Philippines' Cebu Longitudinal Health and Nutrition Survey (CLHNS) is one of the longest running birth cohort studies in Southeast Asia. This paper illustrates the pathways through which maternal and infant nutrition influence later health outcomes using selected CLHNS findings. METHODS: The CLHNS initially examined the determinants and consequences of low birth weight and early nutrition on child growth and development. It has since expanded to study other health, nutrition, and demographic issues in the life course of the cohort participants such as the consequences of early nutrition on adult health. RESULTS: CLHNS findings have documented important effects of poor maternal nutrition beyond impaired foetal growth (manifested through low birth weight). Mothers who had lower energy intakes and poorer nutritional status during pregnancy had offsprings who were at risk of having higher blood pressure measurements in adolescence. Infants born small at birth were not only more likely to be stunted through adolescence, but were also at greater risk of cardiovascular disease later in life. Among the males, those born thin at birth and have high BMI in adulthood had increased risk of elevated systolic blood pressure. Early infant feeding also had long-term effects on health. Breastfeeding not only protected against morbidity and stunting in childhood, but also lowered the risk of insulin resistance and high triglyceride levels in adulthood among the males. Delayed complementary feeding was associated a with lower risk of overweight in young adulthood. An intergenerational matrilineal effect was also observed among the participants, with maternal birth weight being positively associated with offspring birth weight. CONCLUSION: The CLHNS findings support the WHO recommendations for exclusive breastfeeding until six months, timely introduction of complementary foods, and continued breastfeeding until two years. Since child nutrition begins in utero, programs should focus on improving maternal nutrition during pregnancy to minimise the risk of low birth weight.


Assuntos
Aleitamento Materno/estatística & dados numéricos , Nível de Saúde , Inquéritos Epidemiológicos/métodos , Inquéritos Epidemiológicos/estatística & dados numéricos , Fenômenos Fisiológicos da Nutrição do Lactente/fisiologia , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Adulto , Peso ao Nascer , Pressão Sanguínea , Índice de Massa Corporal , Aleitamento Materno/métodos , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Ingestão de Energia/fisiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mães/estatística & dados numéricos , Inquéritos Nutricionais/métodos , Inquéritos Nutricionais/estatística & dados numéricos , Estado Nutricional/fisiologia , Filipinas/epidemiologia
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