Association between a rare SNP in the second intron of human Agouti related protein gene and increased BMI

<p>Abstract</p> <p>Background</p> <p>The agouti related protein (AGRP) is an endogenous antagonist of the melanocortin 4 receptor and is one of the most potent orexigenic factors. The aim of the present study was to assess the genetic variability of <it>AGRP </it>gene and investigate whether the previously reported SNP rs5030980 and the rs11575892, a SNP that so far has not been studied with respect to obesity is associated with increased body mass index (BMI).</p> <p>Methods</p> <p>We determined the complete sequence of the <it>AGRP </it>gene and upstream promoter region in 95 patients with severe obesity (BMI > 35 kg/m²). Three polymorphisms were identified: silent mutation c.123G>A (rs34123523) in the second exon, non-synonymous mutation c.199G>A (rs5030980) and c.131-42C>T (rs11575892) located in the second intron. We further screened rs11575892 in a selected group of 1135 and rs5030980 in group of 789 participants from the Genome Database of Latvian Population and Latvian State Research Program Database.</p> <p>Results</p> <p>The CT heterozygotes of rs11575892 had significantly higher mean BMI value (p = 0.027). After adjustment for age, gender and other significant non-genetic factors (presence of diseases), the BMI levels remained significantly higher in carriers of the rs11575892 T allele (p = 0.001). The adjusted mean BMI value of CC genotype was 27.92 ± 1.01 kg/m²(mean, SE) as compared to 30.97 ± 1.03 kg/m²for the CT genotype. No association was found between rs5030980 and BMI.</p> <p>Conclusion</p> <p>This study presents an association of rare allele of <it>AGRP </it>polymorphism in heterozygous state with increased BMI. The possible functional effects of this polymorphism are unclear but may relate to splicing defects.</p

Child Mortality in Rural Malawi: HIV Closes the Survival Gap between the Socio-Economic Strata

BACKGROUND: As HIV-related deaths increase in a population the usual association between low socioeconomic status and child mortality may change, particularly as death rates from other causes decline. METHODS/PRINCIPAL FINDINGS: As part of a demographic surveillance system in northern Malawi in 2002-6, covering a population of 32,000, information was collected on socio-economic status of the households. Deaths were classified as HIV/AIDS-related or not by verbal autopsy. Poisson regression models were used to assess the association of socio-economic indicators with all-cause mortality, AIDS-mortality and non-AIDS mortality among children. There were 195 deaths in infants, 109 in children aged 1-4 years, and 38 in children aged 5-15. All-cause child mortality in infants and 1-4 year olds was similar in households with higher and lower socio-economic status. In infants 13% of deaths were attributed to AIDS, and there were no clear trends with socio-economic status for AIDS or non-AIDS causes. For 1-4 year olds 27% of deaths were attributed to AIDS. AIDS mortality was higher among those with better built houses, and lowest in those with income from farming and fishing, whereas non-AIDS mortality was higher in those with worse built houses, lowest in those with income from employment, and decreased with increasing household assets. CONCLUSIONS/SIGNIFICANCE: In this population, since HIV infection among adults was initially more common among the less poor, childhood mortality patterns have changed. The usual gap in survival between the poor and the less poor has been lost, but because the less poor have been disproportionately affected by HIV, rather than because of relative improvement in the survival of the poorest

Energy consumption in chemical fuel-driven self-assembly

Nature extensively exploits high-energy transient self-assembly structures that are able to perform work through a dissipative process. Often, self-assembly relies on the use of molecules as fuel that is consumed to drive thermodynamically unfavourable reactions away from equilibrium. Implementing this kind of non-equilibrium self-assembly process in synthetic systems is bound to profoundly impact the fields of chemistry, materials science and synthetic biology, leading to innovative dissipative structures able to convert and store chemical energy. Yet, despite increasing efforts, the basic principles underlying chemical fuel-driven dissipative self-assembly are often overlooked, generating confusion around the meaning and definition of scientific terms, which does not favour progress in the field. The scope of this Perspective is to bring closer together current experimental approaches and conceptual frameworks. From our analysis it also emerges that chemically fuelled dissipative processes may have played a crucial role in evolutionary processes

Non-Hodgkin's lymphoma, obesity and energy homeostasis polymorphisms

A population-based case–control study of lymphomas in England collected height and weight details from 699 non-Hodgkin's lymphoma (NHL) cases and 914 controls. Obesity, defined as a body mass index (BMI) over 30 kg m−2 at five years before diagnosis,, was associated with an increased risk of NHL (OR=1.5, 95% CI 1.1–2.1). The excess was most pronounced for diffuse large B-cell lymphoma (OR=1.9, 95% CI 1.3–2.8). Genetic variants in the leptin (LEP 19G>A, LEP −2548G>A) and leptin receptor genes (LEPR 223Q>R), previously shown to modulate NHL risk, as well as a polymorphism in the energy regulatory gene adiponectin (APM1 276G>T), were investigated. Findings varied with leptin genotype, the risks being decreased with LEP 19AA (OR=0.7, 95% CI 0.5–1.0) and increased with LEP −2548GA (OR=1.3, 95% CI 1.0–1.7) and −2548AA (OR=1.4, 95% CI 1.0–1.9), particularly for follicular lymphoma. These genetic findings, which were independent of BMI, were stronger for men than women

The relationship of telomere length to baseline corticosterone levels in nestlings of an altricial passerine bird in natural populations

Artículo de publicación ISIBackground: Environmental stressors increase the secretion of glucocorticoids that in turn can shorten telomeres via oxidative damage. Modification of telomere length, as a result of adversity faced early in life, can modify an individual's phenotype. Studies in captivity have suggested a relationship between glucocorticoids and telomere length in developing individuals, however less is known about that relationship in natural populations. Methods: In order to evaluate the effect of early environmental stressors on telomere length in natural populations, we compared baseline corticosterone (CORT) levels and telomere length in nestlings of the same age. We collected blood samples for hormone assay and telomere determination from two geographically distinct populations of the Thorn-tailed Rayadito (Aphrastura spinicauda) that differed in brood size; nestlings body mass and primary productivity. Within each population we used path analysis to evaluate the relationship between brood size, body mass, baseline CORT and telomere length. Results: Within each distinct population, path coefficients showed a positive relationship between brood size and baseline CORT and a strong and negative correlation between baseline CORT and telomere length. In general, nestlings that presented higher baseline CORT levels tended to present shorter telomeres. When comparing populations it was the low latitude population that presented higher levels of baseline CORT and shorter telomere length. Conclusions: Taken together our results reveal the importance of the condition experienced early in life in affecting telomere length, and the relevance of integrative studies carried out in natural conditions.FONDECYT Grant 11130245 FONDECYT 1140548 USA National Science Foundation Grant IOS-0750540 ICM-005-002 PFB-23-CONICY

Applying the Salutogenic Framework to Nutrition Research and Practice

Much research has identified a sea of factors related to unhealthy diets to make sense of why people struggle to eat healthy diets. However, little is known of factors that empower healthy eating. Antonovsky's salutogenesis provides an innovative framework to study these factors and identify resources and mechanisms underlying healthy eating practices. We give recommendations for future research and provide examples of how salutogenesis has inspired our own research to gain new insights into the origins of healthy eating. Lastly, implications of using future findings in designing novel nutrition promotion strategies are outlined