Postpartum amenorrhea duration by sex of the newborn in two natural fertility populations.

OBJECTIVES: Postpartum amenorrhea (PA) affects the length of interbirth intervals and thus is intimately related to human life history strategies. PA duration appears to be influenced by maternal energetic status. In humans, as in other mammals, sons are costlier than daughters. Thus, we hypothesize that, in energetically constrained environments, a newborn's sex should be associated with PA duration. METHODS: We analyzed data from two natural fertility populations in which mothers have differing energy budgets: Qom women (n = 121) from a periurban village in Argentina, who have a comparatively calorically dense diet and are sedentary (prepregnancy mean BMI = 24.8 ± 4.5 kg/m2 in 1997), and agropastoral Kaqchikel Maya women (n = 88), who have a comparatively calorically restricted diet and high physical activity levels (mean BMI = 21.8 ± 3.7 kg/m2 ). We predict that (a) mothers of sons exhibit longer PA duration than mothers of daughters and (b) this association between offspring sex and PA duration is stronger in the Maya, who have smaller energy budgets. RESULTS: Maya mothers with sons exhibited estimated mean and median PA durations that were 1.34 times the estimated mean and median PA duration of mothers with daughters (p = 0.02). Among the Qom, mean, and median PA duration did not differ significantly in relation to offspring sex (p = 0.94). CONCLUSIONS: Maya mothers with sons exhibited longer PA duration than those with daughters. This phenomenon was not observed in the well-nourished Qom, possibly due to "buffering" effects from larger energy budgets. Offspring sex may influence birth spacing and maternal life history strategies in energetically constrained environments.

Coal smoke, gestational cadmium exposure, and fetal growth.

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 5000 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 95 g (95% CI: 34, 155 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.

Associations of methylenetetrahydrofolate reductase C677T genotype with blood pressure levels in Chinese population with essential hypertension.

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.

Association of peripheral differential leukocyte counts with dyslipidemia risk in Chinese patients with hypertension: insight from the China Stroke Primary Prevention Trial.

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.

Methylenetetrahydrofolate reductase C677T polymorphism, hypertension and risk of stroke: a prospective, nested case-control study.

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.

Antineoplastic drug contamination in the urine of Canadian healthcare workers.

PURPOSE: The purpose of this study was to quantify the urine concentration of non-metabolized cyclophosphamide (CP), a commonly administered antineoplastic drug, among potentially exposed Canadian healthcare workers and to identify factors associated with the drug concentration levels. METHODS: Participants were asked to provide two sets of 24-h urine samples (at two different sampling events), and the level of CP was quantified using high-performance liquid chromatography-tandem mass spectrometry. In addition to demographic information, participants were surveyed regarding their frequency of handling of antineoplastic drugs, safe drug handling training, and known contact with CP on their work shift. Descriptive and inferential statistical analyses were performed. A backward stepwise linear mixed effect model was conducted to identify the factors associated with urine concentration levels. RESULTS: We collected 201 urine samples, and 55 % (n = 111) had levels greater than the LOD of 0.05 ng/mL. The mean urinary CP concentration was 0.156 ng/mL, the geometric mean was 0.067 ng/mL, the geometric standard deviation was 3.18, the 75th percentile was 0.129 ng/mL, and the range was

Older adults' outdoor walking and the built environment: does income matter?

BACKGROUND: Our aim was to examine the association between Street Smart Walk Score® and self-reported outdoor walking among older Canadians, and to determine whether socioeconomic status modifies this association. METHODS: We linked objective walkability data with cross-sectional survey data from the Canadian Community Health Survey Healthy-Aging 2008-2009 Cycle for a sample of 1309 British Columbians aged ≥ 65 years. We examined associations between Street Smart Walk Score and meeting physical activity guidelines (≥150 min of moderate to vigorous activity/week) through self-reported outdoor walking using multivariable logistic regression, and tested for significant interactions with household income. RESULTS: A ten point higher Street Smart Walk Score was associated with a 17 % higher odds of meeting physical activity guidelines through walking outside (95 % CI: 1.07,1.27). In addition, older adults living in neighbourhoods categorised as Walker's Paradise were over three times more likely to meet guidelines than those living in Car-dependent/Very car dependent neighbourhoods. We found no evidence that household income moderated the effect of Walk Score on walking outside. CONCLUSIONS: Neighbourhood design may be one avenue whereby physical activity levels of older people can be enhanced through outdoor walking, with benefit across socioeconomic strata.

Associations between perfluoroalkyl acids (PFASs) and maternal thyroid hormones in early pregnancy: a population-based cohort study.

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.

Antineoplastic drug contamination on the hands of employees working throughout the hospital medication system.

We previously reported that antineoplastic drug contamination is found on various work surfaces situated throughout the hospital medication system (process flow of drug within a facility from initial delivery to waste disposal). The presence of drug residual on surfaces suggests that healthcare workers involved in some capacity with the system may be exposed through dermal contact. The purpose of this paper was to determine the dermal contamination levels of healthcare employees working throughout a hospital and to identify factors that may influence dermal contamination. We selected participants from six hospitals and wiped the front and back of workers' hands. Wipe samples were analyzed for cyclophosphamide (CP), a commonly used antineoplastic drug, using high-performance liquid chromatography-tandem mass spectrometry. Participants were asked about their frequency of handling antineoplastic drugs, known contact with CP on their work shift, gender, job title, and safe drug handling training. In addition, participants were surveyed regarding their glove usage and hand washing practices prior to wipe sample collection. We collected a total of 225 wipe samples. Only 20% (N = 44) were above the limit of detection (LOD) of 0.36ng per wipe. The average concentration was 0.36ng per wipe, the geometric mean < LOD, the geometric standard deviation 1.98, and the range < LOD to 22.8ng per wipe. Hospital employees were classified into eight different job categories and all categories had some dermal contamination levels in excess of the LOD. The job category with the highest proportion of samples greater than the LOD were those workers in the drug administration unit who were not responsible for drug administration (volunteer, oncologist, ward aide, dietician). Of note, the highest recorded concentration was from a worker who had no known contact with CP on their work shift. Our results suggest that a broader range of healthcare workers than previously believed, including those that do not directly handle or administer the drugs (e.g. unit clerks, ward aides, dieticians, and shipper/receivers), are at risk of exposure to antineoplastic drugs. A review of control measures to minimize antineoplastic drug exposure that encompasses a wide array of healthcare workers involved with the hospital medication system is recommended.

Antineoplastic drug contamination of surfaces throughout the hospital medication system in Canadian hospitals.

We previously reported that there is a potential for antineoplastic drug contamination throughout the hospital medication system (process flow of drug within a facility from delivery to waste disposal) due to the various surfaces contacted by health care workers. This article describes the contamination of these frequently contacted surfaces as well as identifies factors that may be associated with surface contamination. Surfaces which health care workers frequently contact were wiped and the concentration of cyclophosphamide (CP) was determined using high-performance liquid chromatography-tandem mass spectrometry. Descriptive and inferential statistical analyses were performed. A backward stepwise multiple linear regression was conducted to identify determinants associated with surface contamination. Overall, 229 surfaces were sampled, most on two occasions, for a total of 438 surface wipes. The mean CP concentration was 0.201 ng/cm(2), the geometric mean 0.019 ng/cm(2), and the geometric standard deviation 2.54, with a range of less than detection (LOD) to 26.1 ng/cm(2). (Method LOD was 0.356 ng/wipe; factoring in the surface area of the wiped surface, results in a sample LOD ranging from 0.00 to 0.049 ng/cm(2)). Our study found that frequently contacted surfaces at every stage of the hospital medication system had measureable levels of antineoplastic drug contamination. Two factors were statistically significant with respect to their association with surface contamination: (1) the stage of the hospital medication system, and (2) the number of job categories responsible for drug transport. The drug preparation stage had the highest average contamination. Those hospitals that had two or more drug transport job categories had higher levels of surface contamination. Neither the reported handling of CP prior to wipe sampling nor the cleaning of surfaces appeared to be associated with contamination.

Investigating maternal risk factors as potential targets of intervention to reduce socioeconomic inequality in small for gestational age: a population-based study.

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.

Associations of Two Common Polymorphisms in MTHFR Gene with Blood Lipids and Therapeutic Efficacy of Simvastatin.

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.

Relationships to land as a determinant of wellness for Indigenous women, two-spirit, trans, and gender diverse people of reproductive age in Toronto, Canada.

OBJECTIVE: Disparities in Indigenous reproductive health reflect Canada's historic and ongoing colonial relationship with Indigenous peoples, which includes persistent inequities in health and social services. Reproductive justice scholars and activists advocate for intersectional approaches to enhancing Indigenous health equity that recognize land as a central determinant of wellness. The purpose of this study is to examine the association between relationships to land and wellness in a study of urban Indigenous women, two-spirit, trans, and gender diverse people of reproductive age in Canada's largest city, Toronto. METHODS: Data were obtained from the cross-sectional Our Health Counts (OHC) Toronto study, which employed respondent-driven sampling methods (n = 323) and a community-directed comprehensive health assessment survey. In an exploratory analysis, we took an Indigenous reproductive justice theoretical approach to multivariable logistic regression. RESULTS: After adjusting for covariates, there was a statistically significant positive association between relationships to the land and wellness that was estimated with good precision (OR 3.7, 95% CI 2.5-5.3). CONCLUSION: Our findings indicate that among urban Indigenous women, two-spirit, trans, and gender diverse people of reproductive age there is a positive association between feeling strong in their relationships to land and feeling balanced in the four domains of health (physical, spiritual, mental, and emotional). The community-based, community-directed design of OHC Toronto was congruent with a reproductive justice approach to research. Reproductive justice theories are adaptable to quantitative research on Indigenous reproductive health and can yield novel insights for supporting Indigenous wellness.

RéSUMé: OBJECTIF: Les disparités que connaissent les peuples autochtones sur le plan de la santé reproductive sont le reflet des relations coloniales historiques et continues du Canada avec ces peuples, encore entachées d'iniquités dans les domaines de la santé et des services sociaux. Théoricien·nes et militant·es de la justice reproductive préconisent des approches intersectionnelles pour améliorer l'équité en santé chez les peuples autochtones, approches qui reconnaissent le territoire comme un déterminant central du bien-être. Nous avons voulu examiner l'association entre les relations avec le territoire et le bien-être dans une étude menée auprès de femmes et de personnes autochtones bispirituelles, trans et de diverses identités de genre en âge de procréer vivant à Toronto, la plus grande ville du Canada. MéTHODE: Nos données proviennent de l'étude transversale Our Health Counts (OHC) Toronto, qui a employé des méthodes d'échantillonnage en fonction des répondant·es (n = 323) et une enquête d'évaluation globale de la santé dirigée par la communauté. Dans une analyse exploratoire, nous avons employé la régression logistique multivariée selon une approche théorique de justice reproductive autochtone. RéSULTATS: Après l'apport d'ajustements pour tenir compte des covariables, nous avons observé une association positive significative entre les relations avec le territoire et le bien-être, que nous avons estimée avec une bonne précision (RC 3,7, IC de 95 % 2,5­5,3). CONCLUSION: D'après nos constatations, il y a chez les femmes et les personnes autochtones bispirituelles, trans et de diverses identités de genre en âge de procréer vivant en milieu urbain une association positive entre un fort sentiment d'appartenance au territoire et un sentiment d'équilibre entre les quatre domaines de la santé (physique, spirituel, mental et émotionnel). L'étude OHC Toronto ayant été conçue par et pour la communauté, elle est conforme à une approche de recherche axée sur la justice reproductive. Les théories de la justice reproductive peuvent être adaptées à la recherche quantitative sur la santé reproductive autochtone, et elles peuvent jeter un nouvel éclairage sur les moyens d'appuyer le bien-être des personnes autochtones.

Effect of ABCG1 gene DNA methylations on the lipid-lowering efficacy of simvastatin.

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.

The effect of ABCA1 gene DNA methylation on blood pressure levels in a Chinese hyperlipidemic population.

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.

Portable HEPA filter air cleaner use during pregnancy and children's body mass index at two years of age: The UGAAR randomized controlled trial.

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.

Serum folate and DDT isomers and metabolites are inversely associated in Chinese women: a cross-sectional analysis.

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.

Association of surrogate and direct measures of adiposity with risk of metabolic syndrome in rural Chinese women.

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.

Assessing the Relation between Plasma PCB Concentrations and Elevated Autistic Behaviours using Bayesian Predictive Odds Ratios.

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 3⁻4 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: 2008⁻2011). We quantified the concentrations of 6 PCB congeners that were detected in >40% of plasma samples collected during the 1st trimester. At age 3⁻4 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.

Evaluation of random forest regression and multiple linear regression for predicting indoor fine particulate matter concentrations in a highly polluted city.

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 (R2 = 50.2%, R2 = 48.9% respectively). The blended MLR model that included RFR predictions had the best performance (cross validation R2 = 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.