| 1. |
- Newton-Cheh, Christopher, et al.
(författare)
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Genome-wide association study identifies eight loci associated with blood pressure
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:6, s. 666-676
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Tidskriftsartikel (refereegranskat)abstract
- 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 2.5 million 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 eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 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.
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| 2. |
- Szatmari, Peter, et al.
(författare)
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Mapping autism risk loci using genetic linkage and chromosomal rearrangements.
- 2007
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 319-328
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
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| 3. |
- Nag, Amitabh, et al.
(författare)
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First versus subsequent return-stroke current and field peaks in negative cloud-to-ground lightning discharges
- 2008
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 113:D19, s. D19112-
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Tidskriftsartikel (refereegranskat)abstract
- We examine relative magnitudes of electric field peaks of first and subsequent return strokes in negative cloud-to-ground lightning flashes recorded in Florida, Austria, Brazil, and Sweden. On average, the electric field peak of the first stroke is appreciably, 1.7 to 2.4 times, larger than the field peak of the subsequent stroke ( except for studies in Austria where the ratio varies from 1.0 to 2.3, depending on methodology and instrumentation). Similar results were previously reported from electric field studies in Florida, Sweden, and Sri Lanka. For comparison, directly measured peak currents for first strokes are, on average, a factor of 2.3 to 2.5 larger than those for subsequent strokes. There are some discrepancies between first versus subsequent stroke intensities reported from different studies based on data reported by lightning locating systems (LLS). The ratio of LLS-reported peak currents for first and subsequent strokes confirmed by video records is 1.7 to 2.1 in Brazil, while in the United States ( Arizona, Texas, Oklahoma, and the Great Plains) it varies from 1.1 to 1.6, depending on methodology used. The smaller ratios derived from the LLS studies are likely to be due to poor detection of relatively small subsequent strokes. The smaller values in Austria are possibly related ( at least in part) to the higher percentage ( about 50% versus 24-38% in other studies) of flashes with at least one subsequent stroke greater than the first. The effects of excluding single-stroke flashes or subsequent strokes in newly formed channels appear to be relatively small.
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| 4. |
- Ren, Hongzu, et al.
(författare)
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Evidence for the involvement of xenobiotic-responsive nuclear receptors in transcriptional effects upon perfluoroalkyl acid exposure in diverse species
- 2009
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Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 27:3-4, s. 266-277
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Tidskriftsartikel (refereegranskat)abstract
- Humans and ecological species have been found to have detectable body burdens of a number of perfluorinated alkyl acids (PFAA) including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). In mouse and rat liver these compounds elicit transcriptional and phenotypic effects similar to peroxisome proliferator chemicals (PPC) that work through the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα). Recent studies indicate that along with PPARα other nuclear receptors are required for transcriptional changes in the mouse liver after PFOA exposure including the constitutive activated receptor (CAR) and pregnane X receptor (PXR) that regulate xenobiotic metabolizing enzymes (XME). To determine the potential role of CAR/PXR in mediating effects of PFAAs in rat liver, we performed a meta-analysis of transcript profiles from published studies in which rats were exposed to PFOA or PFOS. We compared the profiles to those produced by exposure to prototypical activators of CAR, (phenobarbital (PB)), PXR (pregnenolone 16 alpha-carbonitrile (PCN)), or PPARα (WY-14,643 (WY)). As expected, PFOA and PFOS elicited transcript profile signatures that included many known PPARα target genes. Numerous XME genes were also altered by PFOA and PFOS but not WY. These genes exhibited expression changes shared with PB or PCN. Reexamination of the transcript profiles from the livers of chicken or fish exposed to PFAAs indicated that PPARα, CAR, and PXR orthologs were not activated. Our results indicate that PFAAs under these experimental conditions activate PPARα, CAR, and PXR in rats but not chicken and fish. Lastly, we discuss evidence that human populations with greater CAR expression have lower body burdens of PFAAs.
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| 5. |
- Secin, Fernando P, et al.
(författare)
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Multi-institutional Study of Symptomatic Deep Venous Thrombosis and Pulmonary Embolism in Prostate Cancer Patients Undergoing Laparoscopic or Robot-Assisted Laparoscopic Radical Prostatectomy
- 2008
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 53:1, s. 134-145
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The true incidence of symptomatic deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients undergoing laparoscopic radical prostatectomy is unknown. Our aim was to determine the incidence of symptomatic DVT and PE and the risk factors for these complications. METHODS: Fourteen surgeons from 13 referral institutions from both Europe and the United States provided retrospective data for all 5951 patients treated with laparoscopic radical prostatectomy (LRP), with or without robotic assistance, since the start of their institution's experience. Symptomatic DVT and PE within 90 d of surgery were regarded as venous thromboembolism (VTE). DVT was diagnosed mostly by Doppler ultrasound or contrast venography and PE by lung ventilation/perfusion scan or chest computed tomography or both. Statistical analysis included evaluation of incidence of symptomatic DVT and PE and risk factors as determined by exact methods and logistic regression. RESULTS: Of 5951 patients in the study, 31 developed symptomatic VTE (0.5%; 95% confidence interval [CI], 0.4%, 0.7%). Among patients with an event, 22 (71%) had DVT only, 4 had PE without identified DVT, and 5 had both. Two patients died of PE. Prior DVT (odds ratio [OR]=13.5; 95%CI, 1.4, 61.3), current tobacco smoking (OR=2.8; 95%CI, 1.0, 7.3), larger prostate volume (OR=1.18; 95%CI, 1.09, 1.28), patient re-exploration (OR=20.6; 95%CI, 6.6, 54.0), longer operative time (OR=1.05; 95%CI, 1.02, 1.09), and longer hospital stay (OR=1.05; 95%CI, 1.01, 1.09) were associated with VTE in univariate analysis. Neoadjuvant therapy, body mass index, surgical experience, surgical approach, pathologic stage, perioperative transfusion, and heparin administration were not significant predictors. CONCLUSIONS: The incidence of symptomatic VTE after LRP is low. These data do not support the administration of prophylactic heparin to all patients undergoing LRP, especially those without risk factors for VTE.
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