The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females.

A preponderance of females develop autoimmune disease, including juvenile idiopathic arthritis (JIA), yet the reason for this bias remains elusive. Evidence suggests that genetic risk of disease may be influenced by sex. PTPN22 rs2476601 is associated with JIA and numerous other autoimmune diseases, and has been reported to show female-specific association with type 1 diabetes. We performed main effect and sex-stratified association analyses to determine whether a sex-specific association exists in JIA. As expected, rs2476601 was associated with JIA in our discovery (413 cases and 690 controls) and replication (1008 cases and 9284 controls) samples. Discovery sample sex-stratified analyses demonstrated an association specifically in females (odds ratio (OR)=2.35, 95% confidence interval (CI)=1.52-3.63, P=0.00011) but not males (OR=0.91, 95% CI=0.52-1.60, P=0.75). This was similarly observed in the replication sample. There was evidence for genotype-by-sex interaction (Pinteraction=0.009). The association between rs2476601 and JIA appears restricted to females, partly accounting for the predominance of females with this disease.

The effect of known cardiovascular risk factors on carotid-femoral pulse wave velocity in school-aged children: a population based twin study.

Childhood cardiovascular risk factors affect vascular function long before overt cardiovascular disease. Twin studies provide a unique opportunity to examine the influence of shared genetic and environmental influences on childhood cardiovascular function. We examined the relationship between birth parameters, markers of adiposity, insulin resistance, lipid profile and blood pressure and carotid-femoral pulse wave velocity (PWV), a validated non-invasive measure of arterial stiffness in a healthy cohort of school-aged twin children. PWV was performed on a population-based birth cohort of 147 twin pairs aged 7-11 years. Fasting blood samples, blood pressure and adiposity measures were collected concurrently. Mixed linear regression models were used to account for twin clustering, within- and between-twin pair associations. There were positive associations between both markers of higher adiposity, insulin resistance, elevated triglycerides and PWV, which remained significant after accounting for twin birth-set clustering. There was a positive association between both diastolic and mean arterial blood pressure and PWV in within-pair analysis in dizygotic, but not monozygotic twins, indicating genetic differences evident in dizygotic not monozygotic twins may affect these associations. Increased blood pressure, triglycerides and other metabolic markers are associated with increased PWV in school-aged twins. These results support both the genetic and environmental contribution to higher PWV, as a marker of arterial stiffness, and reiterate the importance of preventing metabolic syndrome from childhood.

The effect of maternal prenatal smoking and alcohol consumption on the placenta-to-birth weight ratio.

BACKGROUND: Maternal influence on fetal growth is mediated through the placenta and this influence may have an implication for the offspring's long-term health. The placenta-to-birth weight ratio has been regarded as an indicator of placental function. However, few studies have examined the effect of maternal lifestyle exposures on the placenta-to-birth weight ratio. This study aims to examine the associations of maternal prenatal smoking and alcohol consumption with the placenta-to-birth weight ratio. METHODS: Data for 7945 term singletons, gestation≥37 weeks, were selected from the Tasmanian Infant Health Survey; a 1988-1995 Australian cohort study. Placenta and birth weight were extracted from birth notification records. RESULTS: Maternal smoking during pregnancy was strongly associated with a 6.77 g/kg higher (95% CI 4.83-8.71) placenta-to-birth weight ratio when compared to non-smoking mothers. Maternal prenatal smoking was associated with lower placental (ß = -15.37 g; 95% CI -23.43 to -7.31) and birth weights (ß = -205.49 g; 95% CI -232.91 to -178.08). Mothers who consumed alcohol during pregnancy had a lower placenta-to-birth weight ratio (ß = -2.07 g/kg; 95% CI -4.01 to -0.12) than mothers who did not consume alcohol. The associations of maternal alcohol consumption during pregnancy with placental and birth weight did not reach statistical significance. DISCUSSION: Maternal prenatal smoking and alcohol consumption may influence fetal growth by either directly or indirectly altering the function of the placenta. CONCLUSIONS: The alteration of the in utero environment induced by smoking and alcohol consumption appears to affect placental and fetal growth in differing ways. Further studies are needed to elucidate the mechanism.

Effects of school-based interventions for direct delivery of physical activity on fitness and cardiometabolic markers in children and adolescents: a systematic review of randomized controlled trials.

UNLABELLED: To evaluate the effectiveness of school-based physical activity interventions on fitness, adiposity and cardiometabolic outcomes among schoolchildren. Medline, Embase, EBSCOhost CINAHL and ERIC databases were searched up to October 2012. INCLUSION CRITERIA: intervention delivered at school with controls having no intervention or usual physical education classes; participants aged 5-18 years; outcomes spanning some or all of the above. We assessed levels of evidence for identified trials based on methodological quality and sample size. Dose of the interventions (a total summary measure of intensity, frequency and duration) were considered. Eighteen randomized controlled trials (RCTs, total participants = 6,207) were included, of which six were large, higher quality trials with high dose of the intervention. The intervention was consistent in increasing fitness with large, higher quality studies and high dose of intervention providing strong evidence. Dose of school-based physical activity is an important determinant of trial efficiency. Some large, higher quality RCTs provided strong evidence for interventions to decrease skin-fold thickness, increase fitness and high-density lipoprotein cholesterol. Evidence for body mass index, body fat and waist circumference, blood pressure and triglycerides, low-density lipoprotein cholesterol and total cholesterol remain inconclusive and require additional higher quality studies with high dose of interventions to provide conclusive evidence.

Maternal and infant factors associated with neonatal adiposity: results from the Tasmanian Infant Health Survey (TIHS).

OBJECTIVE: To examine the maternal and neonatal factors associated with offspring adiposity and the role of birth and placental weight as potential mediators in such associations. DESIGN: The Tasmanian Infant Health Survey was a prospective cohort study conducted between 1988 and 1995 in Australia to investigate the cause of Sudden Infant Death Syndrome. This large infant cohort provides measurement of skinfolds on 7945 mothers and their offspring. SUBJECTS: Participants included singletons born ≥37 weeks gestation who were at high risk of sudden infant death syndrome identified through a composite score that included birth weight, maternal age, neonatal gender, season of birth, duration of second-stage labor and intention to breastfeed. MEASUREMENTS: Neonatal adiposity was assessed from skinfold measurements of the subscapular (SSF) and triceps folds (TSF) taken at birth. Maternal early-pregnancy body mass index (BMI) was calculated from self-reported height and weight. Neonatal data were extracted from birth records. Data relating to other environmental exposures were obtained from questionnaires administered when neonates were ∼4-days old. RESULTS: In multivariable models, higher maternal adiposity, increasing maternal age, gestation age, delivery by Caesarian section and female gender were associated with larger SSF independent of placental and birth weight (P<0.001). Maternal age and delivery by Caesarian section were significantly associated with larger TSF, whereas gestational age and male gender were associated with thinner TSF independent of placental and birth weight. Higher early-pregnancy BMI, maternal weight gain, maternal age, parity and gestational age were significantly associated with larger placental and birth weight. Smoking during pregnancy was associated with smaller birth weight but not with placental weight. CONCLUSION: In addition to birth weight, maternal adiposity and placental weight were important additional factors associated with neonatal adiposity.

Association of change in daily step count over five years with insulin sensitivity and adiposity: population based cohort study.

OBJECTIVES: To investigate the association between change in daily step count and both adiposity and insulin sensitivity and the extent to which the association between change in daily step count and insulin sensitivity may be mediated by adiposity. DESIGN: Population based cohort study. SETTING: Tasmania, Australia. PARTICIPANTS: 592 adults (men (n=267), mean age 51.4 (SD 12.2) years; women (n=325), mean age 50.3 (12.3) years) who participated in the Tasmanian component of the national AusDiab Study in 2000 and 2005. MAIN OUTCOME MEASURES: Body mass index, waist to hip ratio, and HOMA insulin sensitivity at follow-up in 2005. RESULTS: Over the five year period, the daily step count decreased for 65% (n=382) of participants. Having a higher daily step count in 2005 than in 2000 was independently associated with lower body mass index (0.08 (95% confidence interval 0.04 to 0.12) lower per 1000 steps), lower waist to hip ratio (0.15 (0.07 to 0.23) lower), and greater insulin sensitivity (1.38 (0.14 to 2.63) HOMA units higher) in 2005. The mean increase in HOMA units fell to 0.34 (-0.79 to 1.47) after adjustment for body mass index in 2005. CONCLUSIONS: Among community dwelling, middle aged adults, a higher daily step count at five year follow-up than at baseline was associated with better insulin sensitivity. This effect seems to be largely mediated through lower adiposity.

Maternal antenatal peanut consumption and peanut and rye sensitization in the offspring at adolescence.

BACKGROUND: There is considerable controversy whether maternal peanut ingestion during pregnancy might influence sensitization in later life. Objective To examine whether maternal peanut ingestion during pregnancy might increase sensitization in the offspring. METHODS: A population-based longitudinal cohort study with 16 years follow-up was conducted (N=373). Subjects were recruited at birth as part of an infant health study. Maternal antenatal peanut consumption was documented at birth and peanut and rye sensitization were determined by measurement of serum-specific IgE at age 16. RESULTS: Peanut sensitization was common (14%). In the entire cohort (n=310), there was no association between antenatal peanut ingestion and peanut sensitization (P=0.17). However, there was a strong association between antenatal peanut ingestion and decreased risk of rye sensitization and peanut sensitization in those (n=201) without a family history (FH) of asthma (Rye OR 0.30, 95% CI 0.14-0.63, P=0.001 and Peanut OR 0.18, 95% CI 0.04-0.78, P=0.02). There was an increased risk of rye sensitization in those (n=108) with a FH of asthma and antenatal peanut ingestion (Rye OR 2.69, 95% CI 1.11-6.51 P=0.03). It was considered that these sensitizations were likely to be related to the presence of IgE antibodies to cross-reacting carbohydrate epitopes common to rye and peanut allergens. CONCLUSIONS AND CLINICAL RELEVANCE: Antenatal peanut ingestion may influence the development of IgE antibody to cross-reacting carbohydrate epitopes in later life. Genetic factors may modify this association.