排序方式: 共有31条查询结果,搜索用时 287 毫秒
11.
Toxicity of pyrazole and 4-methylpyrazole in mice and rats 总被引:2,自引:0,他引:2
12.
Helgadottir A Manolescu A Helgason A Thorleifsson G Thorsteinsdottir U Gudbjartsson DF Gretarsdottir S Magnusson KP Gudmundsson G Hicks A Jonsson T Grant SF Sainz J O'Brien SJ Sveinbjornsdottir S Valdimarsson EM Matthiasson SE Levey AI Abramson JL Reilly MP Vaccarino V Wolfe ML Gudnason V Quyyumi AA Topol EJ Rader DJ Thorgeirsson G Gulcher JR Hakonarson H Kong A Stefansson K 《Nature genetics》2006,38(1):68-74
Variants of the gene ALOX5AP (also known as FLAP) encoding arachidonate 5-lipoxygenase activating protein are known to be associated with risk of myocardial infarction. Here we show that a haplotype (HapK) spanning the LTA4H gene encoding leukotriene A4 hydrolase, a protein in the same biochemical pathway as ALOX5AP, confers modest risk of myocardial infarction in an Icelandic cohort. Measurements of leukotriene B4 (LTB4) production suggest that this risk is mediated through upregulation of the leukotriene pathway. Three cohorts from the United States also show that HapK confers a modest relative risk (1.16) in European Americans, but it confers a threefold larger risk in African Americans. About 27% of the European American controls carried at least one copy of HapK, as compared with only 6% of African American controls. Our analyses indicate that HapK is very rare in Africa and that its occurrence in African Americans is due to European admixture. Interactions with other genetic or environmental risk factors that are more common in African Americans are likely to account for the greater relative risk conferred by HapK in this group. 相似文献
13.
Thorgeirsson TE Geller F Sulem P Rafnar T Wiste A Magnusson KP Manolescu A Thorleifsson G Stefansson H Ingason A Stacey SN Bergthorsson JT Thorlacius S Gudmundsson J Jonsson T Jakobsdottir M Saemundsdottir J Olafsdottir O Gudmundsson LJ Bjornsdottir G Kristjansson K Skuladottir H Isaksson HJ Gudbjartsson T Jones GT Mueller T Gottsäter A Flex A Aben KK de Vegt F Mulders PF Isla D Vidal MJ Asin L Saez B Murillo L Blondal T Kolbeinsson H Stefansson JG Hansdottir I Runarsdottir V Pola R Lindblad B 《Nature》2008,452(7187):638-642
Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases. 相似文献
14.
A mutation in APP protects against Alzheimer's disease and age-related cognitive decline 总被引:1,自引:0,他引:1
T Jonsson JK Atwal S Steinberg J Snaedal PV Jonsson S Bjornsson H Stefansson P Sulem D Gudbjartsson J Maloney K Hoyte A Gustafson Y Liu Y Lu T Bhangale RR Graham J Huttenlocher G Bjornsdottir OA Andreassen EG Jönsson A Palotie TW Behrens OT Magnusson A Kong U Thorsteinsdottir RJ Watts K Stefansson 《Nature》2012,488(7409):96-99
The prevalence of dementia in the Western world in people over the age of 60 has been estimated to be greater than 5%, about two-thirds of which are due to Alzheimer's disease. The age-specific prevalence of Alzheimer's disease nearly doubles every 5 years after age 65, leading to a prevalence of greater than 25% in those over the age of 90 (ref. 3). Here, to search for low-frequency variants in the amyloid-β precursor protein (APP) gene with a significant effect on the risk of Alzheimer's disease, we studied coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. We found a coding mutation (A673T) in the APP gene that protects against Alzheimer's disease and cognitive decline in the elderly without Alzheimer's disease. This substitution is adjacent to the aspartyl protease β-site in APP, and results in an approximately 40% reduction in the formation of amyloidogenic peptides in vitro. The strong protective effect of the A673T substitution against Alzheimer's disease provides proof of principle for the hypothesis that reducing the β-cleavage of APP may protect against the disease. Furthermore, as the A673T allele also protects against cognitive decline in the elderly without Alzheimer's disease, the two may be mediated through the same or similar mechanisms. 相似文献
15.
G. Magnusson J. -A. Nyberg N. -O. Bodin E. hansson 《Cellular and molecular life sciences : CMLS》1972,28(10):1198-1200
Zusammenfassung Subchronische Gaben von Pyrazol, nicht dagegen von 4-Methylpyrazol, führen bei Ratten und Mäusen zu toxischen Läsionen. 相似文献
16.
Emilsson V Thorleifsson G Zhang B Leonardson AS Zink F Zhu J Carlson S Helgason A Walters GB Gunnarsdottir S Mouy M Steinthorsdottir V Eiriksdottir GH Bjornsdottir G Reynisdottir I Gudbjartsson D Helgadottir A Jonasdottir A Jonasdottir A Styrkarsdottir U Gretarsdottir S Magnusson KP Stefansson H Fossdal R Kristjansson K Gislason HG Stefansson T Leifsson BG Thorsteinsdottir U Lamb JR Gulcher JR Reitman ML Kong A Schadt EE Stefansson K 《Nature》2008,452(7186):423-428
17.
Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
Elks CE Perry JR Sulem P Chasman DI Franceschini N He C Lunetta KL Visser JA Byrne EM Cousminer DL Gudbjartsson DF Esko T Feenstra B Hottenga JJ Koller DL Kutalik Z Lin P Mangino M Marongiu M McArdle PF Smith AV Stolk L van Wingerden SH Zhao JH Albrecht E Corre T Ingelsson E Hayward C Magnusson PK Smith EN Ulivi S Warrington NM Zgaga L Alavere H Amin N Aspelund T Bandinelli S Barroso I Berenson GS Bergmann S Blackburn H Boerwinkle E Buring JE Busonero F Campbell H Chanock SJ Chen W Cornelis MC 《Nature genetics》2010,42(12):1077-1085
To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10???) and 9q31.2 (P = 2.2 × 10?33), we identified 30 new menarche loci (all P < 5 × 10??) and found suggestive evidence for a further 10 loci (P < 1.9 × 10??). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing. 相似文献
18.
Sulem P Gudbjartsson DF Stacey SN Helgason A Rafnar T Magnusson KP Manolescu A Karason A Palsson A Thorleifsson G Jakobsdottir M Steinberg S Pálsson S Jonasson F Sigurgeirsson B Thorisdottir K Ragnarsson R Benediktsdottir KR Aben KK Kiemeney LA Olafsson JH Gulcher J Kong A Thorsteinsdottir U Stefansson K 《Nature genetics》2007,39(12):1443-1452
Hair, skin and eye colors are highly heritable and visible traits in humans. We carried out a genome-wide association scan for variants associated with hair and eye pigmentation, skin sensitivity to sun and freckling among 2,986 Icelanders. We then tested the most closely associated SNPs from six regions--four not previously implicated in the normal variation of human pigmentation--and replicated their association in a second sample of 2,718 Icelanders and a sample of 1,214 Dutch. The SNPs from all six regions met the criteria for genome-wide significance. A variant in SLC24A4 is associated with eye and hair color, a variant near KITLG is associated with hair color, two coding variants in TYR are associated with eye color and freckles, and a variant on 6p25.3 is associated with freckles. The fifth region provided refinements to a previously reported association in OCA2, and the sixth encompasses previously described variants in MC1R. 相似文献
19.
Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes 总被引:1,自引:0,他引:1
Grant SF Thorleifsson G Reynisdottir I Benediktsson R Manolescu A Sainz J Helgason A Stefansson H Emilsson V Helgadottir A Styrkarsdottir U Magnusson KP Walters GB Palsdottir E Jonsdottir T Gudmundsdottir T Gylfason A Saemundsdottir J Wilensky RL Reilly MP Rader DJ Bagger Y Christiansen C Gudnason V Sigurdsson G Thorsteinsdottir U Gulcher JR Kong A Stefansson K 《Nature genetics》2006,38(3):320-323
20.
Catecholamines of the spinal cord normally and after transection 总被引:1,自引:0,他引:1
Zusammenfassung Der Noradrenalingehalt im Rückenmark des Kaninchens beträgt 0.15 µg/g. Eine Querschnittsläsion durch das Rückenmark führt zu einer 90%igen Abnahme des Noradrenalingehaltes. Dies legt die Annahme nahe, dass Noradrenalin in Nervenzellen des Zentralnervensystems lokalisiert ist. Im Gegensatz zu anderen Untersuchern fanden wir im Rückenmark kein Dopamin.
The work has been supported by grants from the Office of Aerospace Research, United States Air Force and the Swedish Medical Research Council. 相似文献
The work has been supported by grants from the Office of Aerospace Research, United States Air Force and the Swedish Medical Research Council. 相似文献