Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5m genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N≤71,225 European ancestry, N=12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N=29,136). We identified association between systolic or diastolic blood pressure and common variants in 8 regions near the CYP17A1 (P=7×10−24), CYP1A2 (P=1×10−23), FGF5 (P=1×10−21), SH2B3 (P=3×10−18), MTHFR (P=2×10−13), c10orf107 (P=1×10−9), ZNF652 (P=5×10−9) and PLCD3 (P=1×10−8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10(-5)) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10(-5)). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10(-10), odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression.

Background Formaldehyde is a ubiquitous pollutant to which humans are exposed. Pathologists can experience high formaldehyde exposure levels. Formaldehyde – among other properties – induce oxidative stress and free radicals, which react with DNA and lipids, leading to oxidative damage and lipid peroxidation, respectively. We measured the levels of air-formaldehyde exposure in a group of Italian pathologists and controls. We analyzed the effect of formaldehyde exposure on leukocyte malondialdehyde-deoxyguanosine adducts (M1-dG), a biomarker of oxidative stress and lipid peroxidation. We studied the relationship between air-formaldehyde and M1-dG adducts. Methods Air-formaldehyde levels were measured by personal air samplers. M1-dG adducts were analyzed by 32P-postlabelling assay. Results Reduction rooms pathologists were significantly exposed to air-formaldehyde in respect to controls and to the pathologists working in other laboratory areas (p<0.001). A significant difference for M1-dG adducts between exposed pathologists and controls was found (p=0.045). The effect becomes stronger when the evaluation of air-formaldehyde exposure was based on personal samplers (p=0.018). Increased M1dG adduct levels were only found in individuals exposed to air-formaldehyde concentrations higher than 66 μg/m3. When the exposed workers and controls were subgrouped according to smoking, M1-dG tended to increase in all the subjects but a significant association between M1-dG and air-formaldehyde was only found in not smokers (p= 0.009). Air formaldehyde played a role positive but not significant (r = 0.355, p = 0.075, Pearson correlation) in the formation of M1-dG, only in not smokers. Conclusions Working in the reduction rooms and to be exposed to air-formaldehyde concentrations higher than 66 μg/m3 is associated with increased levels of M1-dG adducts.

BackgroundAir pollution can cause respiratory symptoms or exacerbate pre-existing respiratory diseases, especially in children. This study looked at the short-term association of air pollution concentrations with Emergency Room (ER) admissions for respiratory reasons in pediatric age (0–18 years).MethodsDaily number of ER admissions in a children’s Hospital, concentrations of urban-background PM2.5, NO2, O3 and total aeroallergens (Corylaceae, Cupressaceae, Gramineae, Urticaceae, Ambrosia, Betula) were collected in Turin, northwestern Italy, for the period 1/08/2008 to 31/12/2010 (883 days). The associations between exposures and ER admissions were estimated, at time lags between 0 and 5 days, using generalized linear Poisson regression models, adjusted for non-meteorological potential confounders.ResultsIn the study period, 21,793 ER admissions were observed, mainly (81 %) for upper respiratory tract infections. Median air pollution concentrations were 22.0, 42.5, 34.1 μg/m3 for urban-background PM2.5, NO2, and O3, respectively, and 2.9 grains/m3 for aeroallergens. We found that ER admissions increased by 1.3 % (95 % CI: 0.3-2.2 %) five days after a 10 μg/m3 increase in NO2, and by 0.7 % (95 % CI: 0.1-1.2 %) one day after a 10 grains/m3 increase in aeroallergens, while they were not associated with PM2.5 concentrations. ER admissions were negatively associated with O3 and aeroallergen concentrations at some time lags, but these association shifted to the null when meteorological confounders were adjusted for in the models.ConclusionsOverall, these findings confirm adverse short-term health effects of air pollution on the risk of ER admission in children and encourage a careful management of the urban environment to health protection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-016-3376-3) contains supplementary material, which is available to authorized users.