Measuring health inequality among children in developing countries: does the choice of the indicator of economic status matter?

Background Currently, poor-rich inequalities in health in developing countries receive a lot of attention from both researchers and policy makers. Since measuring economic status in developing countries is often problematic, different indicators of wealth are used in different studies. Until now, there is a lack of evidence on the extent to which the use of different measures of economic status affects the observed magnitude of health inequalities. Methods This paper provides this empirical evidence for 10 developing countries, using the Demographic and Health Surveys data-set. We compared the World Bank asset index to three alternative wealth indices, all based on household assets. Under-5 mortality and measles immunisation coverage were the health outcomes studied. Poor-rich inequalities in under-5 mortality and measles immunisation coverage were measured using the Relative Index of Inequality. Results Comparing the World Bank index to the alternative indices, we found that (1) the relative position of households in the national wealth hierarchy varied to an important extent with the asset index used, (2) observed poor-rich inequalities in under-5 mortality and immunisation coverage often changed, in some cases to an important extent, and that (3) the size and direction of this change varied per country, index, and health indicator. Conclusion Researchers and policy makers should be aware that the choice of the measure of economic status influences the observed magnitude of health inequalities, and that differences in health inequalities between countries or time periods, may be an artefact of different wealth measures used

Bats Avoid Radar Installations: Could Electromagnetic Fields Deter Bats from Colliding with Wind Turbines?

Large numbers of bats are killed by collisions with wind turbines, and there is at present no direct method of reducing or preventing this mortality. We therefore determine whether the electromagnetic radiation associated with radar installations can elicit an aversive behavioural response in foraging bats. Four civil air traffic control (ATC) radar stations, three military ATC radars and three weather radars were selected, each surrounded by heterogeneous habitat. Three sampling points matched for habitat type and structure, dominant vegetation species, altitude and surrounding land class were located at increasing distances from each station. A portable electromagnetic field meter measured the field strength of the radar at three distances from the source: in close proximity (<200 m) with a high electromagnetic field (EMF) strength >2 volts/metre, an intermediate point within line of sight of the radar (200–400 m) and with an EMF strength <2 v/m, and a control site out of sight of the radar (>400 m) and registering an EMF of zero v/m. At each radar station bat activity was recorded three times with three independent sampling points monitored on each occasion, resulting in a total of 90 samples, 30 of which were obtained within each field strength category. At these sampling points, bat activity was recorded using an automatic bat recording station, operated from sunset to sunrise. Bat activity was significantly reduced in habitats exposed to an EMF strength of greater than 2 v/m when compared to matched sites registering EMF levels of zero. The reduction in bat activity was not significantly different at lower levels of EMF strength within 400 m of the radar. We predict that the reduction in bat activity within habitats exposed to electromagnetic radiation may be a result of thermal induction and an increased risk of hyperthermia

Studies of the Association of Arg72Pro of Tumor Suppressor Protein p53 with Type 2 Diabetes in a Combined Analysis of 55,521 Europeans

A study of 222 candidate genes in type 2 diabetes reported association of variants in RAPGEF1, ENPP1, TP53, NRF1, SLC2A2, SLC2A4 and FOXC2 with type 2 diabetes in 4,805 Finnish individuals. We aimed to replicate these associations in a Danish case-control study and to substantiate any replicated associations in meta-analyses. Furthermore, we evaluated the impact on diabetes-related intermediate traits in a population-based sample of middle-aged Danes.We genotyped nine lead variants in the seven genes in 4,973 glucose-tolerant and 3,612 type 2 diabetes Danish individuals. In meta-analyses we combined case-control data from the DIAGRAM+ Consortium (n = 47,117) and the present genotyping results. The quantitative trait studies involved 5,882 treatment-naive individuals from the Danish Inter99 study.None of the nine investigated variants were significantly associated with type 2 diabetes in the Danish samples. However, for all nine variants the estimate of increase in type 2 diabetes risk was observed for the same allele as previously reported. In a meta-analysis of published and online data including 55,521 Europeans the G-allele of rs1042522 in TP53 showed significant association with type 2 diabetes (OR = 1.06 95% CI 1.02-1.11, p = 0.0032). No substantial associations with diabetes-related intermediary phenotypes were found.The G-allele of TP53 rs1042522 is associated with an increased prevalence of type 2 diabetes in a combined analysis of 55,521 Europeans

Implications of Central Obesity-Related Variants in LYPLAL1, NRXN3, MSRA, and TFAP2B on Quantitative Metabolic Traits in Adult Danes

Two meta-analyses of genome-wide association studies (GWAS) have suggested that four variants: rs2605100 in lysophospholipase-like 1 (LYPLAL1), rs10146997 in neuroxin 3 (NRXN3), rs545854 in methionine sulfoxide reductase A (MSRA), and rs987237 in transcription factor activating enhancer-binding protein 2 beta (TFAP2B) associate with measures of central obesity. To elucidate potential underlying phenotypes we aimed to investigate whether these variants associated with: 1) quantitative metabolic traits, 2) anthropometric measures (waist circumference (WC), waist-hip ratio, and BMI), or 3) type 2 diabetes, and central and general overweight and obesity.The four variants were genotyped in Danish individuals using KASPar®. Quantitative metabolic traits were examined in a population-based sample (n = 6,038) and WC and BMI were furthermore analyzed in a combined study sample (n = 13,507). Case-control studies of diabetes and adiposity included 15,326 individuals. The major G-allele of LYPLAL1 rs2605100 associated with increased fasting serum triglyceride concentrations (per allele effect (β) = 3%(1;5(95%CI)), p(additive) = 2.7×10(-3)), an association driven by the male gender (p(interaction) = 0.02). The same allele associated with increased fasting serum insulin concentrations (β = 3%(1;5), p(additive) = 2.5×10(-3)) and increased insulin resistance (HOMA-IR) (β = 4%(1;6), p(additive) = 1.5×10(-3)). The minor G-allele of rs10146997 in NRXN3 associated with increased WC among women (β = 0.55cm (0.20;0.89), p(additive) = 1.7×10(-3), p(interaction) = 1.0×10(-3)), but showed no associations with obesity related metabolic traits. The MSRA rs545854 and TFAP2B rs987237 showed nominal associations with central obesity; however, no underlying metabolic phenotypes became obvious, when investigating quantitative metabolic traits. None of the variants influenced the prevalence of type 2 diabetes.We demonstrate that several of the central obesity-associated variants in LYPLAL1, NRXN3, MSRA, and TFAP2B associate with metabolic and anthropometric traits in Danish adults. However, analyses were made without adjusting for multiple testing, and further studies are needed to confirm the putative role of LYPLAL1, NRXN3, MSRA, and TFAP2B in the pathophysiology of obesity

The minor C-allele of rs2014355 in ACADS is associated with reduced insulin release following an oral glucose load

<p>Abstract</p> <p>Background</p> <p>A genome-wide association study (GWAS) using metabolite concentrations as proxies for enzymatic activity, suggested that two variants: rs2014355 in the gene encoding short-chain acyl-coenzyme A dehydrogenase (<it>ACADS</it>) and rs11161510 in the gene encoding medium-chain acyl-coenzyme A dehydrogenase (<it>ACADM</it>) impair fatty acid β-oxidation. Chronic exposure to fatty acids due to an impaired β-oxidation may down-regulate the glucose-stimulated insulin release and result in an increased risk of type 2 diabetes (T2D). We aimed to investigate whether the two variants associate with altered insulin release following an oral glucose load or with T2D.</p> <p>Methods</p> <p>The variants were genotyped using KASPar^®PCR SNP genotyping system and investigated for associations with estimates of insulin release and insulin sensitivity following an oral glucose tolerance test (OGTT) in a random sample of middle-aged Danish individuals (<it>n</it>_{<it>ACADS </it>}= 4,324; <it>n</it>_{<it>ACADM </it>}= 4,337). The T2D-case-control study involved a total of ~8,300 Danish individuals (<it>n</it>_{<it>ACADS </it>}= 8,313; <it>n</it>_{<it>ACADM </it>}= 8,344).</p> <p>Results</p> <p>In glucose-tolerant individuals the minor C-allele of rs2014355 of <it>ACADS </it>associated with reduced measures of serum insulin at 30 min following an oral glucose load (per allele effect (β) = -3.8% (-6.3%;-1.3%), <it>P </it>= 0.003), reduced incremental area under the insulin curve (β = -3.6% (-6.3%;-0.9%), <it>P </it>= 0.009), reduced acute insulin response (β = -2.2% (-4.2%;0.2%), <it>P </it>= 0.03), and with increased insulin sensitivity ISI_Matsuda(β = 2.9% (0.5%;5.2%), <it>P </it>= 0.02). The C-allele did not associate with two other measures of insulin sensitivity or with a derived disposition index. The C-allele was not associated with T2D in the case-control analysis (OR 1.07, 95% CI 0.96-1.18, <it>P </it>= 0.21). rs11161510 of <it>ACADM </it>did not associate with any indices of glucose-stimulated insulin release or with T2D.</p> <p>Conclusions</p> <p>In glucose-tolerant individuals the minor C-allele of rs2014355 of <it>ACADS </it>was associated with reduced measures of glucose-stimulated insulin release during an OGTT, a finding which in part may be mediated through an impaired β-oxidation of fatty acids.</p

Bioinformatics-Driven Identification and Examination of Candidate Genes for Non-Alcoholic Fatty Liver Disease

ObjectiveCandidate genes for non-alcoholic fatty liver disease (NAFLD) identified by a bioinformatics approach were examined for variant associations to quantitative traits of NAFLD-related phenotypes.Research Design and MethodsBy integrating public database text mining, trans-organism protein-protein interaction transferal, and information on liver protein expression a protein-protein interaction network was constructed and from this a smaller isolated interactome was identified. Five genes from this interactome were selected for genetic analysis. Twenty-one tag single-nucleotide polymorphisms (SNPs) which captured all common variation in these genes were genotyped in 10,196 Danes, and analyzed for association with NAFLD-related quantitative traits, type 2 diabetes (T2D), central obesity, and WHO-defined metabolic syndrome (MetS).Results273 genes were included in the protein-protein interaction analysis and EHHADH, ECHS1, HADHA, HADHB, and ACADL were selected for further examination. A total of 10 nominal statistical significant associations (P&lt;0.05) to quantitative metabolic traits were identified. Also, the case-control study showed associations between variation in the five genes and T2D, central obesity, and MetS, respectively. Bonferroni adjustments for multiple testing negated all associations.ConclusionsUsing a bioinformatics approach we identified five candidate genes for NAFLD. However, we failed to provide evidence of associations with major effects between SNPs in these five genes and NAFLD-related quantitative traits, T2D, central obesity, and MetS

Ageing, adipose tissue, fatty acids and inflammation

A common feature of ageing is the alteration in tissue distribution and composition, with a shift in fat away from lower body and subcutaneous depots to visceral and ectopic sites. Redistribution of adipose tissue towards an ectopic site can have dramatic effects on metabolic function. In skeletal muscle, increased ectopic adiposity is linked to insulin resistance through lipid mediators such as ceramide or DAG, inhibiting the insulin receptor signalling pathway. Additionally, the risk of developing cardiovascular disease is increased with elevated visceral adipose distribution. In ageing, adipose tissue becomes dysfunctional, with the pathway of differentiation of preadipocytes to mature adipocytes becoming impaired; this results in dysfunctional adipocytes less able to store fat and subsequent fat redistribution to ectopic sites. Low grade systemic inflammation is commonly observed in ageing, and may drive the adipose tissue dysfunction, as proinflammatory cytokines are capable of inhibiting adipocyte differentiation. Beyond increased ectopic adiposity, the effect of impaired adipose tissue function is an elevation in systemic free fatty acids (FFA), a common feature of many metabolic disorders. Saturated fatty acids can be regarded as the most detrimental of FFA, being capable of inducing insulin resistance and inflammation through lipid mediators such as ceramide, which can increase risk of developing atherosclerosis. Elevated FFA, in particular saturated fatty acids, maybe a driving factor for both the increased insulin resistance, cardiovascular disease risk and inflammation in older adults

Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.Peer reviewe

Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery