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BACKGROUND: Gestational cadmium exposure may impair fetal growth. Coal smoke has largely been unexplored as a source of cadmium exposure. We investigated the relationship between gestational cadmium exposure and fetal growth, and assessed coal smoke as a potential source of airborne cadmium, among non-smoking pregnant women in Ulaanbaatar, Mongolia, where coal combustion in home heating stoves is a major source of outdoor and indoor air pollution. METHODS: This observational study was nested within the Ulaanbaatar Gestation and Air Pollution Research (UGAAR) study, a randomized controlled trial of portable high efficiency particulate air (HEPA) filter air cleaner use during pregnancy, fetal growth, and early childhood development. We measured third trimester blood cadmium concentrations in 374 out of 465 participants who had a live birth. We used multiple linear and logistic regression to assess the relationships between log2-transformed maternal blood cadmium concentrations and birth weight, length, head circumference, ponderal index, low birth weight, small for gestational age, and preterm birth in crude and adjusted models. We also evaluated the relationships between log2-transformed blood cadmium concentrations and the density of coal-burning stoves within 5000â¯m of each participant's apartment as a proxy of coal smoke emissions from home heating stoves. RESULTS: The median (25th,75th percentile) blood cadmium concentration was 0.20 (0.15, 0.29) µg/L. A doubling of blood cadmium was associated with a 95â¯g (95% CI: 34, 155â¯g) reduction in birth weight in adjusted models. An interquartile range increase in coal stove density (from 3.4 to 4.9 gers/hectare) surrounding participants' apartments was associated with a 12.2% (95% CI: 0.3, 25.6%) increase in blood cadmium concentrations. CONCLUSIONS: Gestational cadmium exposure was associated with reduced birth weight. In settings where coal is a widely used fuel, cadmium may play a role in the putative association between air pollution and impaired fetal growth.
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Contaminantes Atmosféricos/toxicidad , Cadmio/toxicidad , Carbón Mineral/toxicidad , Desarrollo Fetal/efectos de los fármacos , Contaminación del Aire/estadística & datos numéricos , Peso al Nacer , Niño , Preescolar , Femenino , Humanos , Recién Nacido , Exposición Materna/estadística & datos numéricos , Mongolia , Material Particulado , EmbarazoRESUMEN
OBJECTIVE: To confirm the association between baseline blood pressure (BP) levels and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism in patients with essential hypertension. METHODS: A total of 347 patients were enrolled from the Dongzhi community in Anhui Province, China. The C677T polymorphism of the MTHFR gene was detected using high-throughput TaqMan allelic discrimination assay. Baseline BP was measured using a standardized mercury-gravity monometer. RESULTS: In the whole sample, the frequency of the MTHFR C677T genotypes CC, CT, and TT were 38.6%, 48.1%, and 13.3%, respectively. In a recessive model (CC+CT versus TT genotypes), baseline diastolic blood pressure (DBP) was significantly higher in patients with the TT genotype compared to those with the CT or CC genotypes (P= 0.013). We also divided all patients into three groups based on the tertiles of the baseline BP distribution. Compared to subjects in the lowest tertile of DBP, the adjusted odds of having the TT genotype among subjects in the highest tertile was 2.6 (95% CI: 1.1 to 6.2). However, no significant associations were observed between baseline systolic blood pressure (SBP) and the MTHFR C677T polymorphism. CONCLUSIONS: The MTHFR gene polymorphism could be an important genetic determinant of baseline DBP levels in Chinese essential hypertensive patients.
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Pueblo Asiatico/genética , Presión Sanguínea/genética , Hipertensión Esencial/genética , Hipertensión Esencial/fisiopatología , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Adulto , Alelos , China , Diástole/genética , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Sístole/genéticaRESUMEN
The aim of the present study was to examine the association between peripheral differential leukocyte counts and dyslipidemia in a Chinese hypertensive population. A total of 10,866 patients with hypertension were enrolled for a comprehensive assessment of cardiovascular risk factors using data from the China Stroke Primary Prevention Trial. Plasma lipid levels and total leukocyte, neutrophil, and lymphocyte counts were determined according to standard methods. Peripheral differential leukocyte counts were consistently and positively associated with serum total cholesterol (TC), LDL cholesterol (LDL-C), and TG levels (all P < 0.001 for trend), while inversely associated with HDL cholesterol levels (P < 0.05 for trend). In subsequent analyses where serum lipids were dichotomized (dyslipidemia/normolipidemia), we found that patients in the highest quartile of total leukocyte count (≥7.6 × 109 cells/l) had 1.64 times the risk of high TG [95% confidence interval (CI): 1.46, 1.85], 1.34 times the risk of high TC (95% CI: 1.20, 1.50), and 1.24 times the risk of high LDL-C (95% CI: 1.12, 1.39) compared with their counterparts in the lowest quartile of total leukocyte count. Similar patterns were also observed with neutrophils and lymphocytes. In summary, these findings indicate that elevated differential leukocyte counts are directly associated with serum lipid levels and increased odds of dyslipidemia.
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Enfermedades Cardiovasculares/sangre , Dislipidemias/sangre , Hipertensión/sangre , Recuento de Leucocitos , Anciano , Enfermedades Cardiovasculares/patología , China , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Dislipidemias/genética , Dislipidemias/patología , Femenino , Humanos , Hipertensión/genética , Hipertensión/patología , Lípidos/sangre , Masculino , Persona de Mediana Edad , Factores de Riesgo , Triglicéridos/sangreRESUMEN
BACKGROUND: Hyperhomocysteinemia is a risk factor for cardiovascular disease. To date, limited prospective studies have examined the joint effects of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, hyperhomocysteinemia and conventional vascular risk factors on risk of stroke and stroke death. METHODS: A total of 39 165 subjects from nine communities within Anqing, Anhui Province, China were prospectively followed from March 1995 to April 2005, with an average follow-up period of 6.2 years. None of the subjects had any history of vascular events at baseline. At follow-up, 251 incident stroke cases were identified. Using a nested, case-control study design, this analysis includes 106 cases with complete MTHFR C677T genotyping data and plasma samples. We selected 106 controls without vascular events matched for age, sex, community and years of plasma storage. Plasma total homocysteine (tHcy) level was measured by high-performance liquid chromatography. RESULTS: Hypertension was independently associated with incident stroke and stroke death after adjusting for important covariates including plasma log-transformed Hcy level. Relative to non-carriers of the MTHFR 677TT genotype with no hypertension, the adjusted odds ratio (95% confidence interval) of stroke and stroke death among hypertensive carriers of the MTHFR 677TT genotype was 10.6 (3.2 to 34.8), 5.8 (1.6 to 21.3), respectively. After excluding subjects with plasma Hcy above 20 µmol/L, the relative odds for stroke, but not for stroke death, was more significantly pronounced (OR = 24.1, 95% CI: 2.3 to 246.1) among subjects with moderate plasma Hcy levels. However, there was no significant interactive effect between hypertensive status and the MTHFR C677T variant on the odds of the two outcomes as estimated by interaction models. CONCLUSIONS: Our major findings suggest that joint effects of the MTHFR C677T polymorphism and hypertension are consistent in predicting a significantly high risk of stroke. In addition for moderate plasma levels of Hcy, the predicted effects on the risk for the primary end point of stroke were more pronounced. These results may help to modify current approaches to vascular disease prevention in Chinese hypertensive patients.
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Predisposición Genética a la Enfermedad/genética , Hipertensión/epidemiología , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/genética , Adulto , Anciano , Estudios de Casos y Controles , China/epidemiología , Ayuno/sangre , Femenino , Genotipo , Homocisteína/sangre , Humanos , Hipertensión/enzimología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Accidente Cerebrovascular/enzimologíaRESUMEN
BACKGROUND: Associations between perfluoroalkyl acids (PFASs) and human thyroid hormone levels remain unclear, especially during early pregnancy when small changes in maternal thyroid hormones can affect fetal brain development. OBJECTIVES: To examine associations between maternal serum PFAS levels and maternal thyroid hormone levels in the early 2nd trimester of pregnancy. METHODS: Participants were euthyroid pregnant women (n=152) enrolled in the Chemicals, Health and Pregnancy (CHirP) study based in Vancouver, Canada. Associations between maternal serum PFASs, including perfluorohexanesulfonate (PFHxS), perfluorononanoate (PFNA), perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) and repeated measures of maternal thyroid hormones, including free thyroxine (fT4), total thyroxine (TT4) and thyroid stimulating home (TSH) were examined using mixed effects linear models. Associations were considered in all women, then separately in women with high (≥ 9 IU/mL) vs normal (<9 IU/mL) levels of thyroid peroxidase antibody (TPOAb), a marker of autoimmune hypothyroidism (Hashimoto's disease). RESULTS: Median PFAS concentrations (ng/mL) in maternal sera were 1.0 (PFHxS), 0.6 (PFNA), 1.7 (PFOA) and 4.8 (PFOS). PFASs were not associated with fT4, TT4 or TSH among women with normal TPOAb. However, among the 9% of women with high TPOAb (n=14), interquartile range (IQR) increases of PFASs were associated with a 46-69% increase in maternal TSH (95% CIs ranging from 8% to 123%) (PFNA, PFOA and PFOS only), and with a 3% to 7% decrease in maternal fT4 (95% CIs ranging from -18% to 5%) (all 4 PFASs). PFNA was also associated with higher maternal TSH in the whole sample. CONCLUSIONS: PFASs were positively associated with TSH, and weakly negatively associated with fT4 in the subset of pregnant women with high TPOAb, which occurs in 6-10% of pregnancies. PFASs may exacerbate the already high TSH and low fT4 levels in these women during early pregnancy, which is a critical time of thyroid hormone-mediated fetal brain development. The clinical significance of these findings is not clear. We propose a "multiple hit hypothesis" to explain these findings; this hypothesis deserves evaluation in larger, more representative study samples.
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Ácidos Alcanesulfónicos/sangre , Contaminantes Ambientales/sangre , Tirotropina/sangre , Tiroxina/sangre , Adolescente , Adulto , Caprilatos/sangre , Estudios de Cohortes , Femenino , Fluorocarburos/sangre , Humanos , Embarazo , Segundo Trimestre del Embarazo/sangre , Ácidos Sulfónicos/sangre , Adulto JovenRESUMEN
BACKGROUND: The major aim of this study was to investigate whether maternal risk factors associated with socioeconomic status and small for gestational age (SGA) might be viable targets of interventions to reduce differential risk of SGA by socioeconomic status (socioeconomic SGA inequality) in the metropolitan area of Vancouver, Canada. METHODS: This study included 59,039 live, singleton births in the Vancouver Census Metropolitan Area (Vancouver) from January 1, 2006 to September 17, 2009. To identify an indicator of socioeconomic SGA inequality, we used hierarchical logistic regression to model SGA by area-level variables from the Canadian census. We then modelled SGA by area-level average income plus established maternal risk factors for SGA and calculated population attributable SGA risk percentages (PAR%) for each variable. Associations of maternal risk factors for SGA with average income were investigated to identify those that might contribute to SGA inequality. Finally, we estimated crude reductions in the percentage and absolute differences in SGA risks between highest and lowest average income quintiles that would result if interventions on maternal risk factors successfully equalized them across income levels or eliminated them altogether. RESULTS: Average income produced the most linear and statistically significant indicator of socioeconomic SGA inequality with 8.9% prevalence of SGA in the lowest income quintile compared to 5.6% in the highest. The adjusted PAR% of SGA for variables were: bottom four quintiles of height (51%), first birth (32%), bottom four quintiles of average income (14%), oligohydramnios (7%), underweight or hypertension, (6% each), smoking (3%) and placental disorder (1%). Shorter height, underweight and smoking during pregnancy had higher prevalence in lower income groups. Crude models assuming equalization of risk factors across income levels or elimination altogether indicated little potential change in relative socioeconomic SGA inequality and reduction in absolute SGA inequality for shorter height only. CONCLUSIONS: Our findings regarding maternal height may indicate trans-generational aetiology for socioeconomic SGA inequalities and/or that adult height influences social mobility. Conditions affecting foetal and childhood growth might be viable targets to reduce absolute socioeconomic SGA inequality in future generations, but more research is needed to determine whether such an approach is appropriate.
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Disparidades en el Estado de Salud , Recién Nacido Pequeño para la Edad Gestacional , Clase Social , Adulto , Colombia Británica , Femenino , Humanos , Recién Nacido , Modelos Logísticos , Oportunidad Relativa , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Cardio-cerebrovascular disease is an important public health challenge worldwide, and its complex etiology has not been elucidated fully. The study investigated the relationship between two common polymorphisms, C677T and A1298C in the methylenetetrahydrofolate reductase (MTHFR) gene, baseline lipids and the lipid-lowering efficacy of simvastatin in a Chinese hyperlipidemic population. METHODS: All participants were recruited from Anhui, China. By the extreme sampling method, we selected subjects with a low response (n=108) and high response (n=106) based on their adjusted lipid-lowering response to simvastatin administrated for 8 consecutive weeks. Both MTHFR C677T and A1298C loci were genotyped by the MALDI-TOF MS platform. Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured at baseline and after 8 weeks of oral 20 mg/d tablets of simvastatin. RESULTS: Patients with the 677TT genotype had significantly higher baseline TC, HDL-C, and change in HDL-C (ΔHDL-C) levels after treatment than those with 677CC+CT genotypes (ß = 0.207, P = 0.045; ß = 0.182, P = 0.026; and ß = 0.16, P = 0.002, respectively). Patients with 1298AC+CC genotypes had significantly higher baseline LDL-C and change in LDL-C (ΔLDL-C) levels (ß = 0.276, P =0.043; ß = 0.359, P = 0.025, respectively) than those with 1298AA genotype. We found statistical interactions between the two SNPs in association with baseline HDL-C (P for interaction = 0.034), TC (P for interaction = 0.069), and TG (P for interaction = 0.034). Baseline TC (P = 0.027) and HDL-C (P = 0.046) and change in HDL-C (P = 0.019) were different among those with the MTHFR A-T haplotype compared with A-C. CONCLUSION: Our major findings suggest that both MTHFR C677T and A1298C polymorphisms could be important genetic determinants of lipid traits and drug efficacy of simvastatin. This will contribute to a better understanding of strategies for personalized medication in Chinese patients with dyslipidemia.
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Dislipidemias , Metilenotetrahidrofolato Reductasa (NADPH2) , Simvastatina , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Dislipidemias/tratamiento farmacológico , Dislipidemias/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Lípidos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo de Nucleótido Simple , Simvastatina/uso terapéuticoRESUMEN
Aim: We investigated the effect of ABCG1 gene DNA methylation in the lipid-lowering efficacy of simvastatin. Materials & methods: An extreme sampling approach was used to select 211 individuals from the top and bottom 15% of adjusted lipid-lowering response residuals to simvastatin after eight consecutive weeks. DNA methylation was measured before treatment by the MethylTarget bisulfite sequencing method. Results:ABCG1_A DNA methylations were negatively associated with baseline high-density lipoprotein cholesterol (HDL-C) and the change in HDL-C after treatment. ABCG1_C methylations were also related to the change in triglyceride and HDL-C. Moreover, mean ABCG1_A and ABCG1_C methylations explain 7.2% of the ΔTC (total cholesterol) and 17.5% of the ΔHDL-C level variability, respectively. Conclusion: DNA methylations at the ABCG1 gene play significant inhibitory effects in the lipid-lowering therapy of simvastatin.
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Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/genética , Anticolesterolemiantes/uso terapéutico , Metilación de ADN/efectos de los fármacos , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/genética , Simvastatina/uso terapéutico , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/metabolismo , Adulto , Anticolesterolemiantes/farmacología , HDL-Colesterol/antagonistas & inhibidores , HDL-Colesterol/sangre , Metilación de ADN/fisiología , Femenino , Humanos , Hiperlipidemias/sangre , Lípidos/antagonistas & inhibidores , Lípidos/sangre , Masculino , Persona de Mediana Edad , Simvastatina/farmacología , Resultado del TratamientoRESUMEN
Hypertension is an important public health challenge worldwide. Epigenetic studies are providing novel insight into the underlying mechanisms of hypertension. We investigated the effect of DNA methylation in ATP-binding cassette transporter 1 (ABCA1) gene on blood pressure levels in a Chinese hyperlipidemic population. We randomly selected 211 individuals with hyperlipidemia who had not received any lipid-lowering treatment at baseline from our previous statin pharmacogenetics study (n = 734). DNA methylation loci at the ABCA1 gene were measured by MethylTarget, a next generation bisulfite sequencing-based multiple targeted cytosine-guanine dinucleotide methylation analysis method. Mean DNA methylation level was used in statistical analysis. In all subjects, higher mean ABCA1_B methylation was positively associated with systolic blood pressure (SBP) (ß = 8.27, P = 0.008; ß = 8.78, P = 0.005) and explained 2.7% and 5.8% of SBP variation before and after adjustment for lipids, respectively. We further divided all patients into three groups based on the tertile of body mass index (BMI) distribution. In the middle tertile of BMI, there was a significantly positive relationship between mean ABCA1_A methylation and SBP (ß = 0.89, P = 0.003) and DBP (ß = 0.32, P = 0.030). Mean ABCA1_A methylation explained 11.0% of SBP variation and 5.3% of DBP variation, respectively. Furthermore, mean ABCA1_A methylation (ß = 0.79; P = 0.007) together with age and gender explained up to 24.1% of SBP variation. Our study provides new evidence that the ABCA1 DNA methylation profile is associated with blood pressure levels, which highlights that DNA methylation might be a significant molecular mechanism involved in the pathophysiological process of hypertension.
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Metilación de ADN , Transportador 1 de Casete de Unión a ATP/genética , Presión Sanguínea/genética , China/epidemiología , HumanosRESUMEN
IMPORTANCE: Gestational exposure to particulate matter (PM) air pollution may increase the risk of childhood obesity, but the impact of reducing air pollution during pregnancy on obesity-related outcomes in childhood has not been examined. OBJECTIVE: To assess the impact of reducing gestational PM exposure on body mass index (BMI) at two years of age. METHODS: In this single-blind, parallel group randomized controlled trial in Ulaanbaatar Mongolia, we randomly assigned 540 pregnant women to receive 1-2 portable high efficiency particulate air (HEPA) filter air cleaners or no air cleaners. We measured height and weight when children were a mean age of 23.8 months. Our primary outcome was age- and sex-specific BMI z-score based on the World Health Organization 2007 Growth Charts. Secondary outcomes included age- and sex-specific weight z score, overweight/obesity (defined as BMI z-score > 2.00), and catch-up growth (defined using various cut-offs to identify children with relatively low birth weight for sex and gestational age and relatively high age- and sex-specific weight in childhood). We imputed missing outcome data using multiple imputation with chained equations and our primary analysis was by intention to treat (ITT). We estimated intervention effects on continuous and binary outcomes using linear and logistic regression, respectively. RESULTS: After excluding known miscarriages, still births, and neonatal deaths our analysis included 480 children (235 control and 245 intervention). The mean (SD) child BMI z score was 0.79 (1.0); 9.8% of children were overweight or obese. The mean BMI z score of children who were randomly assigned to the intervention group was 0.16-units lower (95% CI: -0.35, 0.04) than children in the control group. The intervention was also associated with reductions in overweight/obesity (odds ratio = 0.59; 95% CI: 0.31, 1.12). Catch-up growth occurred less frequently in the intervention group, but effect estimates varied depending on the specific definition of catch-up growth and confidence intervals consistently spanned no effect. CONCLUSIONS: We found that the use of portable air cleaners during pregnancy was associated with improvements in obesity-related outcomes, although some effect estimates lacked precision. Reducing PM exposure during pregnancy may lead to improvements in cardiometabolic health in childhood.
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Filtros de Aire , Contaminación del Aire , Obesidad Infantil , Índice de Masa Corporal , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Sobrepeso , Obesidad Infantil/epidemiología , Obesidad Infantil/prevención & control , Embarazo , Método Simple CiegoRESUMEN
BACKGROUND: Vitamin nutritional status may influence some xenobiotic metabolism or vice versa. METHODS: This analysis examines the relationship between B-vitamin concentrations and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDT) isomers and metabolites in healthy women. Serum pp'DDT, pp'DDE, pp'DDD, op'DDT, op'DDE, and serum folate, cysteine, and vitamins B6 and B12 were measured in 296 nonsmoking female textile workers (21-34 yr) in Anhui, China. Mean (SD) age and body mass index of this cohort were 24.9 (1.5) y and 19.7 (2.0) kg/m(2), respectively. RESULTS: Median pp'DDT, pp'DDE, pp'DDD, op'DDT, and op'DDE were 1.5, 29.2, 0.22, 0.17, and 0.09 ng/g, respectively. Median folate and cysteine were 9.2 and 200.0 nmol/L, respectively. Folate was significantly inversely associated with pp'DDT and pp'DDE: beta (95% confidence interval [CI]) = -0.23 (-0.39, -0.07) and -0.20 (-0.36, -0.05), respectively, and it was marginally associated with pp'DDD. Cysteine was significantly inversely associated with pp'DDT, beta (95% CI) = -0.69 (-1.00, -0.37); pp'DDE, beta (95% CI) = -0.32 (-0.62, -0.02); pp'DDD, beta (95% CI) = -0.31 (-0.59, -0.03); and op'DDT, beta (95% CI) = -0.35 (-0.68, -0.02). CONCLUSIONS: Folate and cysteine are independently inversely associated with DDT isomers, adjusting for vitamins B6 and B12, age, and body mass index. These nutrients may play a role in DDT metabolism; however, it is also possible that DDT may exert a negative impact on folate and cysteine levels. Longitudinal studies are needed to ascertain the direction of this association.
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DDT/sangre , Ácido Fólico/sangre , Adulto , China , Estudios Transversales , Cisteína/sangre , Femenino , Humanos , Isomerismo , Modelos Lineales , Estudios Prospectivos , Vitamina B 12/sangre , Vitamina B 6/sangre , Adulto JovenRESUMEN
BACKGROUND: Most studies linking obesity and metabolic syndrome (MS) have used body mass index (BMI) and waist circumference (WC) to measure obesity. While BMI is correlated with direct measures of total and central adiposity, it is influenced by lean body and bone mass. We hypothesize that direct measures of adiposity may help develop further insight into the link between obesity and MS, thus more accurately identifying individuals at high risk for MS. AIM OF THE STUDY: We examined how surrogate and direct measures of adiposity were associated with MS risk and if direct adiposity measures enhanced BMI and WC identification of MS risk. METHODS: 3,734 Chinese female twins aged 20-39 years were studied. Percent body fat (%BF) and proportion of trunk fat to total BF (%TF) were assessed by DEXA. Graphic plots and generalized estimating equations were used to examine the associations of adiposity measures with MS and its components. Concordance of adiposity measures and MS abnormalities between monozygotic (MZ) and dizygotic (DZ) twin pairs were compared. RESULTS: The prevalence of MS increased for high BMI (>or=23 kg/m(2)), %BF (>or=32), WC (>or=80 cm), and (to a lesser degree) %TF (>or=50). Below those thresholds, the prevalence of MS was low (0-5.3%). %TF was independently associated with higher risk of MS and its components even after adjusting for BMI and WC. As a result, among women with normal BMI and WC, high %TF was associated with 1.3-2.0-fold elevated risk of MS components. In contrast, women with high BMI but normal WC and %TF neither have significantly increased risk of MS, nor for any component other than high BP. MZ twins showed higher concordance for MS and its components than DZ twins. CONCLUSIONS: In this lean Chinese rural female sample, BMI >or= 23 and WC >or= 80 were associated with a markedly increased risk of MS, which was further enhanced by elevated %TF. Even in women with a normal BMI and WC, %TF was independently associated with MS and its components. Twin analysis findings suggest that adiposity measurements and MS risk are influenced by genetics.
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Adiposidad , Síndrome Metabólico/epidemiología , Obesidad/epidemiología , Absorciometría de Fotón , Adulto , Composición Corporal , Índice de Masa Corporal , China/epidemiología , Femenino , Humanos , Síndrome Metabólico/complicaciones , Repeticiones de Microsatélite , Obesidad/complicaciones , Oportunidad Relativa , Prevalencia , Medición de Riesgo , Estadísticas no Paramétricas , Encuestas y Cuestionarios , Delgadez , Gemelos Dicigóticos/sangre , Gemelos Monocigóticos/sangre , Circunferencia de la Cintura , Adulto JovenRESUMEN
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social communication and repetitive or stereotypic behaviours. In utero exposure to environmental chemicals, such as polychlorinated biphenyls (PCBs), may play a role in the etiology of ASD. We examined the relation between plasma PCB concentrations measured during pregnancy and autistic behaviours in a subset of children aged 3â»4 years old in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pregnancy and birth cohort of 546 mother-infant pairs from Canada (enrolled: 2008â»2011). We quantified the concentrations of 6 PCB congeners that were detected in >40% of plasma samples collected during the 1st trimester. At age 3â»4 years, caregivers completed the Social Responsiveness Scale-2 (SRS), a valid and reliable measure of children's reciprocal social and repetitive behaviours and restricted interests. We examined SRS scores as both a continuous and binary outcome, and we calculated Bayesian predictive odds ratios for more autistic behaviours based on a latent variable model for SRS scores >60. We found no evidence of an association between plasma PCB concentrations and autistic behaviour. However, we found small and imprecise increases in the mean SRS score and odds of more autistic behaviour for the highest category of plasma PCB concentrations compared with the lowest category; for instance, an average increase of 1.4 (95%PCI: -0.4, 3.2) in the mean SRS (exposure contrast highest versus lowest PCB category) for PCB138 translated to an odds ratio of 1.8 (95%PCI: 1.0, 2.9). Our findings illustrate the importance of measuring associations between PCBs and autistic behaviour on both continuous and binary scales.
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Trastorno del Espectro Autista/inducido químicamente , Contaminantes Ambientales/sangre , Exposición Materna/efectos adversos , Bifenilos Policlorados/sangre , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Trastorno del Espectro Autista/sangre , Teorema de Bayes , Canadá , Estudios de Casos y Controles , Preescolar , Monitoreo del Ambiente , Femenino , Humanos , Masculino , Oportunidad Relativa , Embarazo , Efectos Tardíos de la Exposición Prenatal/sangre , Factores de RiesgoRESUMEN
BACKGROUND: Indoor and outdoor fine particulate matter (PM2.5) are both leading risk factors for death and disease, but making indoor measurements is often infeasible for large study populations. METHODS: We developed models to predict indoor PM2.5 concentrations for pregnant women who were part of a randomized controlled trial of portable air cleaners in Ulaanbaatar, Mongolia. We used multiple linear regression (MLR) and random forest regression (RFR) to model indoor PM2.5 concentrations with 447 independent 7-day PM2.5 measurements and 87 potential predictor variables obtained from outdoor monitoring data, questionnaires, home assessments, and geographic data sets. We also developed blended models that combined the MLR and RFR approaches. All models were evaluated in a 10-fold cross-validation. RESULTS: The predictors in the MLR model were season, outdoor PM2.5 concentration, the number of air cleaners deployed, and the density of gers (traditional felt-lined yurts) surrounding the apartments. MLR and RFR had similar performance in cross-validation (R2â¯=â¯50.2%, R2â¯=â¯48.9% respectively). The blended MLR model that included RFR predictions had the best performance (cross validation R2â¯=â¯81.5%). Intervention status alone explained only 6.0% of the variation in indoor PM2.5 concentrations. CONCLUSIONS: We predicted a moderate amount of variation in indoor PM2.5 concentrations using easily obtained predictor variables and the models explained substantially more variation than intervention status alone. While RFR shows promise for modelling indoor concentrations, our results highlight the importance of out-of-sample validation when evaluating model performance. We also demonstrate the improved performance of blended MLR/RFR models in predicting indoor air pollution.
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Contaminación del Aire Interior/análisis , Exposición Materna , Modelos Teóricos , Material Particulado/análisis , Filtros de Aire , Monitoreo del Ambiente/métodos , Femenino , Humanos , Modelos Lineales , Mongolia , Tamaño de la Partícula , Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto , Estaciones del AñoRESUMEN
We conducted a cross-sectional study to investigate the effects of the adenosine triphosphate-binding cassette transporter 1 (ABCA1) I883M and lipoprotein lipase (LPL) HindIII polymorphisms on lipid levels in patients with hyperlipidemia. A total of 533 patients were enrolled. Serum lipid parameters were determined by an automatic biochemistry analyzer. Genotyping of the ABCA1 I883M and LPL HindIII was carried out using the polymerase chain reaction-restriction fragment length polymorphism technique. Multiple linear regression analysis was used to estimate the associations between serum lipid levels and the genetic polymorphisms. The frequency distribution of the ABCA1 I883M and LPL HindIII polymorphisms did not deviate from Hardy-Weinberg equilibrium. The major finding of our regression analysis showed that neither the ABCA1 I883M nor the LPL HindIII polymorphism was associated with baseline serum lipid levels in the total population. However, among patients with elevated alanine aminotransferase (ALT) levels (ALT ≥ 40 U/L), carriers of the M allele of the ABCA1 gene had lower levels of high-density lipoprotein cholesterol (HDL-C) and higher levels of low-density lipoprotein cholesterol (LDL-C) after adjusting for age, sex, smoking status, alcohol consumption, education level, occupation, and work intensity ( P < .05 for both). A test on interaction terms between the ABCA1 I833M polymorphism and ALT on HDL-C and LDL-C levels also remained significant ( P = .001 and P = .014, respectively). Our data suggest that there are significant interactive effects between ABCA1 I883M and ALT levels on HDL-C and LDL-C levels. However, the LPL HindIII polymorphism did not influence lipid levels.
Asunto(s)
Transportador 1 de Casete de Unión a ATP/genética , Hiperlipidemias/genética , Lípidos/sangre , Lipoproteínas LDL/genética , Polimorfismo Genético , Alanina Transaminasa/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , HumanosRESUMEN
Our goal was to examine the associations of the 388A>G and 521T>C polymorphisms in the solute carrier organic anion transporter 1B1 (SLCO1B1) gene with hepatic function, baseline lipid levels, and the lipid-lowering efficiency of simvastatin. We recruited 542 patients with hyperlipidemia. The 388A>G and 521T>C polymorphisms were genotyped. Serum alanine aminotransferase (ALT) and aspartate transaminase (AST), Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured before and after an oral 20-mg dose of simvastatin. Individuals with the 388AA genotype had higher ALT and AST levels than those with the 388AG or 388GG genotypes (P = .037 and P = .002, respectively). Individuals with both the 388AA and the 521TT genotypes had the highest levels of ALT and AST (P = .001 and P = .001, respectively). Moreover, we divided all patients into normal and abnormal subgroups based on elevated ALT and AST values (≥ 40 U/L), participants in the abnormal subgroup had a higher frequency of the 388A/521T haplotype and a lower frequency of the 388G/521T haplotype compared to those in the normal subgroup. In addition, compared to 388G allele and 521C allele carriers, individuals with the 388G allele and 521TT genotype carriers had greater TC and LDL-C reduction in response to simvastatin after 4 weeks of treatment. Our conclusion suggests that the interaction between the SLCO1B1 388A>G and 521T>C polymorphisms could be an important genetic determinant of hepatic function and the therapeutic efficiency of simvastatin in Chinese patients with hyperlipidemia.
Asunto(s)
Alelos , Haplotipos , Hiperlipidemias , Lípidos/sangre , Transportador 1 de Anión Orgánico Específico del Hígado , Hígado/metabolismo , Polimorfismo Genético , Simvastatina/administración & dosificación , Anciano , Femenino , Humanos , Hiperlipidemias/sangre , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/genética , Hígado/patología , Transportador 1 de Anión Orgánico Específico del Hígado/genética , Transportador 1 de Anión Orgánico Específico del Hígado/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
This study was conducted to explore interactions in the association of the kininogen (KNG1) Ile197Met polymorphism and gender with plasma concentrations of irbesartan in Chinese patients with essential hypertension. A total of 1100 subjects with essential hypertension received a daily oral dose of 150 mg irbesartan for twenty-eight consecutive days. High-performance liquid chromatography-fluorescence (HPLC) was used to detect plasma irbesartan concentrations on day 28. The KNG1 Ile197Met gene polymorphism was determined using high-throughput TaqMan technology. The frequency distribution of KNG1 Ile197Met genotype conformed to the Hardy-Weinberg equilibrium. After 28 days of treatment, patients with the GG genotype had significantly lower irbesartan concentrations (P = 0.033) compared to homozygous TT genotype carriers. After stratifying by gender, male G allele carriers had significantly lower irbesartan concentrations (GG, P = 0.015; TG, P = 0.015, respectively) relative to TT genotype after adjusting for age, region, body mass index (BMI), smoking, and alcohol consumption. However, there was no significant difference in female subjects. A further test for a multiplicative interaction between the KNG1 Ile197Met polymorphism and gender in association with ln-plasma irbesartan concentrations in a multiple linear regression model was also significant (P for interaction = 0.033). This is the first study to suggest that gender may influence the association of the Ile197Met variant of KNG1 with ln-plasma irbesartan concentration. This finding may indicate that the interaction of gender and the KNG1 Ile197Met gene polymorphism can influence plasma trough irbesartan concentrations, which may contribute to a better development of personalized hypertensive treatment in Chinese patients.
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Hipertensión Esencial/genética , Irbesartán/sangre , Quininógenos/genética , Pueblo Asiatico/genética , Hipertensión Esencial/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Farmacogenómica , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Factores SexualesRESUMEN
BACKGROUND: Portable HEPA filter air cleaners can reduce indoor fine particulate matter (PM2.5), but their use has not been adequately evaluated in high pollution settings. We assessed air cleaner effectiveness in reducing indoor residential PM2.5 and second hand smoke (SHS) exposures among non-smoking pregnant women in Ulaanbaatar, Mongolia. METHODS: We randomized 540 participants to an intervention group receiving 1 or 2 HEPA filter air cleaners or a control group receiving no air cleaners. We followed 259 intervention and 253 control participants to the end of pregnancy. We measured one-week indoor residential PM2.5 concentrations in early (~11weeks gestation) and late (~31weeks gestation) pregnancy and collected outdoor PM2.5 data from centrally-located government monitors. We assessed blood cadmium in late pregnancy. Hair nicotine was quantified in a subset (n=125) to evaluate blood cadmium as a biomarker of SHS exposure. We evaluated air cleaner effectiveness using mixed effects and multiple linear regression models and used stratified models and interaction terms to evaluate potential modifiers of effectiveness. RESULTS: The overall geometric mean (GM) one-week outdoor PM2.5 concentration was 47.9µg/m3 (95% CI: 44.6, 51.6µg/m3), with highest concentrations in winter (118.0µg/m3; 110.4, 126.2µg/m3). One-week indoor and outdoor PM2.5 concentrations were correlated (r=0.69). Indoor PM2.5 concentrations were 29% (21, 37%) lower in intervention versus control apartments, with GMs of 17.3µg/m3 (15.8, 18.8µg/m3) and 24.5µg/m3 (22.2, 27.0µg/m3), respectively. Air cleaner effectiveness was greater when air cleaners were first deployed (40%; 31, 48%) than after approximately five months of use (15%; 0, 27%). Blood cadmium concentrations were 14% (4, 23%) lower among intervention participants, likely due to reduced SHS exposure. CONCLUSIONS: Portable HEPA filter air cleaners can lower indoor PM2.5 concentrations and SHS exposures in highly polluted settings.
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Filtros de Aire , Contaminantes Atmosféricos/análisis , Contaminación del Aire/prevención & control , Exposición Materna/estadística & datos numéricos , Contaminación del Aire/estadística & datos numéricos , Contaminación del Aire Interior , Femenino , Filtración , Humanos , Exposición Materna/prevención & control , Mongolia , Embarazo , Contaminación por Humo de Tabaco/análisis , Contaminación por Humo de Tabaco/prevención & control , Contaminación por Humo de Tabaco/estadística & datos numéricosRESUMEN
BACKGROUND: Fine particulate matter (PM2.5) exposure may impair fetal growth. AIMS/OBJECTIVES: Our aim was to assess the effect of portable high efficiency particulate air (HEPA) filter air cleaner use during pregnancy on fetal growth. METHODS: The Ulaanbaatar Gestation and Air Pollution Research (UGAAR) study is a single-blind randomized controlled trial conducted in Ulaanbaatar, Mongolia. Non-smoking pregnant women recruited at ≤18â¯weeks gestation were randomized to an intervention (1-2 air cleaners in homes from early pregnancy until childbirth) or control (no air cleaners) group. Participants were not blinded to their intervention status. Demographic, health, and birth outcome data were obtained via questionnaires and clinic records. We used unadjusted linear and logistic regression and time-to-event analysis to evaluate the intervention. Our primary outcome was birth weight. Secondary outcomes were gestational age-adjusted birth weight, birth length, head circumference, gestational age at birth, and small for gestational age. The study is registered at ClinicalTrials.gov (NCT01741051). RESULTS: We recruited 540 participants (272 control and 268 intervention) from January 9, 2014 to May 1, 2015. There were 465 live births and 28 losses to follow up. We previously reported a 29% (95% CI: 21, 37%) reduction in indoor PM2.5 concentrations with portable HEPA filter air cleaner use. The median (25th, 75th percentile) birth weights for control and intervention participants were 3450â¯g (3150, 3800â¯g) and 3550â¯g (3200, 3800â¯g), respectively (pâ¯=â¯0.34). The intervention was not associated with birth weight (18â¯g; 95% CI: -84, 120â¯g), but in a pre-specified subgroup analysis of 429 term births the intervention was associated with an 85â¯g (95% CI: 3, 167â¯g) increase in mean birth weight. CONCLUSIONS: HEPA filter air cleaner use in a high pollution setting was associated with greater birth weight only among babies born at term.
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Filtros de Aire , Contaminación del Aire/prevención & control , Desarrollo Fetal , Material Particulado , Adulto , Peso al Nacer , Femenino , Edad Gestacional , Humanos , Recién Nacido , Modelos Logísticos , Masculino , Embarazo , Método Simple CiegoRESUMEN
BACKGROUND: There is growing concern that poisoning and other adverse health effects are increasing because organophosphorous (OP) insecticides are now being used in combination with pyrethroid (PYR) insecticides to enhance the toxic effects of PYR insecticides on target insects, especially those that have developed PYR resistance. OBJECTIVES: We conducted a pilot biomonitoring study to determine whether men in our reproductive cohort study were being exposed to pesticides environmentally by virtue of frequenting an agricultural setting. METHODS: We screened 18 randomly selected urine samples collected from male participants of reproductive age for 24 parent compounds and metabolites of pesticides and examined the results in relation to sperm concentration. RESULTS: Results showed high prevalence of exposure to OP and PYR pesticides and our preliminary analyses provided some suggestion that the higher exposure group had lower sperm concentration. CONCLUSIONS: The potential of OP/PYR mixtures to have enhanced human toxicity needs more research attention.