Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldWe recently described an association between risk of type 2diabetes and variants in the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4), with a population attributable risk (PAR) of 17%-28% in three populations of European ancestry. Here, we refine the definition of the TCF7L2 type 2diabetes risk variant, HapB(T2D), to the ancestral T allele of a SNP, rs7903146, through replication in West African and Danish type 2 diabetes case-control studies and an expanded Icelandic study. We also identify another variant of the same gene, HapA, that shows evidence of positive selection in East Asian, European and West African populations. Notably, HapA shows a suggestive association with body mass index and altered concentrations of the hunger-satiety hormones ghrelin and leptin in males, indicating that the selective advantage of HapA may have been mediated through effects on energy metabolism

Pollen Competition as a Reproductive Isolation Barrier Represses Transgene Flow between Compatible and Co-Flowering Citrus Genotypes

Background/Objective: Despite potential benefits granted by genetically modified (GM) fruit trees, their release and commercialization raises concerns about their potential environmental impact, and the transfer via pollen of transgenes to cross-compatible cultivars is deemed to be the greatest source for environmental exposure. Information compiled from field trials on GM trees is essential to propose measures to minimize the transgene dispersal. We have conducted a field trial of seven consecutive years to investigate the maximum frequency of pollen-mediated crop-to-crop transgene flow in a citrus orchard, and its relation to the genetic, phenological and environmental factors involved. Methodology/Principal Findings: Three different citrus genotypes carrying the uidA (GUS) tracer marker gene (pollen donors) and a non-GM self-incompatible contiguous citrus genotype (recipient) were used in conditions allowing natural entomophilous pollination to occur. The examination of 603 to 2990 seeds per year showed unexpectedly low frequencies (0.17-2.86%) of transgene flow. Paternity analyses of the progeny of subsets of recipient plants using 10 microsatellite (SSR) loci demonstrated a higher mating competence of trees from another non-GM pollen source population that greatly limited the mating chance of the contiguous cross-compatible and flowering-synchronized transgenic pollen source. This mating superiority could be explained by a much higher pollen competition capacity of the non-GM genotypes, as was confirmed through mixed-hand pollinations. Conclusions/Significance: Pollen competition strongly contributed to transgene confinement. Based on this finding, suitable isolation measures are proposed for the first time to prevent transgene outflow between contiguous plantings of citrus types that may be extendible to other entomophilous transgenic fruit tree species. (Résumé d'auteur

Vztrajanje pri nedolžnosti otroštva

Prispevek izpostavlja, da ponovno obujanje diskurza nedolžnega otroštva nastopa kot ideološki diskurz in depolitizirana oblika govora o otrocih in otroštvu. Ta ideologija nedolžnosti v času poglobljenega razslojevanja in konsolidacije neoliberalnega kapitalizma odvrača pogled od otroka kot družbeno zaznamovane in kompleksne modalnosti, ki je tudi sam predmet medsebojno soizgradnih razrednih, rasnih, spolnih in etničnih umestitev. Pomembno vlogo pri obujanju ideologije nedolžnega otroštva ima agresivno tržena komercialna literatura, ki s ponovnim vkoreninjanjem ideologije nedolžnega otroštva na eni strani skriva in briše razgled nad družbeno specifičnostjo otroka, po drugi in komplementarni strani pa s tem manevrom otroka istočasno postavlja za odlagališče in skrito varovalo konservativnih vpisov, med drugim tudi omejujočih družbenospolnih shem

The association of bone mineral density measures with incident cardiovascular disease in older men and women: the Health, Aging, and Body Composition Study

Summary: The associations of volumetric and areal bone mineral density (BMD) measures with incident cardiovascular disease (CVD) were studied in a biracial cohort of 2,310 older adults. BMD measures were inversely related to CVD in women and white men, independent of age and shared risk factors for osteoporosis and CVD. Introduction: We investigated the associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with incident cardiovascular disease (CVD) in older adults enrolled in the Health, Aging, and Body Composition study. Methods: The incidence of CVD was ascertained in 2,310 well-functioning white and black participants (42% black; 55% women), aged 68-80 years. aBMD measures of the hip were assessed using DXA. Spine trabecular, integral, and cortical vBMD measures were obtained using QCT. Results: During an average follow-up of 5.4 years, 23% of men and 14% of women had incident CVD. Spine vBMD measures were inversely associated with incident CVD in white men [HR(integral)=1.39, 95% CI 1.03-1.87; HR(cortical)=1.38, 95% CI 1.03-1.84], but not in black men. In women, aBMD measures of the total hip (HR=1.36, 95% CI 1.03-1.78), femoral neck (HR=1.44, 95% CI 1.10-1.90), and trochanter (HR=1.34, 95% CI 1.04-1.72) exhibited significant associations with CVD in blacks, but not in whites. All associations were independent of age and shared risk factors between osteoporosis and CVD, and were not explained by inflammatory cytokines or oxidized LDL. Conclusion: Our results provide support for an inverse association between BMD and incident CVD. Further research should elucidate possible pathophysiological mechanisms linking osteoporosis and CVD. © 2007 International Osteoporosis Foundation and National Osteoporosis Foundation

A variant in CDKAL1 influences insulin response and risk of type 2 diabetes

We conducted a genome-wide association study for type 2 diabetes (T2D) in Icelandic cases and controls, and we found that a previously described variant in the transcription factor 7-like 2 gene (TCF7L2) gene conferred the most significant risk. In addition to confirming two recently identified risk variants, we identified a variant in the CDKAL1 gene that was associated with T2D in individuals of European ancestry (allele-specific odds ratio (OR) = 1.20 (95% confidence interval, 1.13-1.27), P = 7.7 x 10(-9)) and individuals from Hong Kong of Han Chinese ancestry (OR = 1.25 (1.11-1.40), P = 0.00018). The genotype OR of this variant suggested that the effect was substantially stronger in homozygous carriers than in heterozygous carriers. The ORs for homozygotes were 1.50 (1.31-1.72) and 1.55 (1.23-1.95) in the European and Hong Kong groups, respectively. The insulin response for homozygotes was approximately 20% lower than for heterozygotes or noncarriers, suggesting that this variant confers risk of T2D through reduced insulin secretion