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991.
Rosendahl J Witt H Szmola R Bhatia E Ozsvári B Landt O Schulz HU Gress TM Pfützer R Löhr M Kovacs P Blüher M Stumvoll M Choudhuri G Hegyi P te Morsche RH Drenth JP Truninger K Macek M Puhl G Witt U Schmidt H Büning C Ockenga J Kage A Groneberg DA Nickel R Berg T Wiedenmann B Bödeker H Keim V Mössner J Teich N Sahin-Tóth M 《Nature genetics》2008,40(1):78-82
Chronic pancreatitis is a persistent inflammatory disease of the pancreas, in which the digestive protease trypsin has a fundamental pathogenetic role. Here we have analyzed the gene encoding the trypsin-degrading enzyme chymotrypsin C (CTRC) in German subjects with idiopathic or hereditary chronic pancreatitis. Two alterations in this gene, p.R254W and p.K247_R254del, were significantly overrepresented in the pancreatitis group, being present in 30 of 901 (3.3%) affected individuals but only 21 of 2,804 (0.7%) controls (odds ratio (OR) = 4.6; confidence interval (CI) = 2.6-8.0; P = 1.3 x 10(-7)). A replication study identified these two variants in 10 of 348 (2.9%) individuals with alcoholic chronic pancreatitis but only 3 of 432 (0.7%) subjects with alcoholic liver disease (OR = 4.2; CI = 1.2-15.5; P = 0.02). CTRC variants were also found in 10 of 71 (14.1%) Indian subjects with tropical pancreatitis but only 1 of 84 (1.2%) healthy controls (OR = 13.6; CI = 1.7-109.2; P = 0.0028). Functional analysis of the CTRC variants showed impaired activity and/or reduced secretion. The results indicate that loss-of-function alterations in CTRC predispose to pancreatitis by diminishing its protective trypsin-degrading activity. 相似文献
992.
Replication of signals from recent studies of Crohn's disease identifies previously unknown disease loci for ulcerative colitis 总被引:1,自引:0,他引:1
Franke A Balschun T Karlsen TH Hedderich J May S Lu T Schuldt D Nikolaus S Rosenstiel P Krawczak M Schreiber S 《Nature genetics》2008,40(6):713-715
Following up on recent genome-wide association studies (GWAS) of Crohn's disease, we investigated 50 previously reported susceptibility loci in a German sample of individuals with Crohn's disease (n = 1,850) or ulcerative colitis (n = 1,103) and healthy controls (n = 1,817). Among these loci, we identified variants in 3p21.31, NKX2-3 and CCNY as susceptibility factors for both diseases, whereas variants in PTPN2, HERC2 and STAT3 were associated only with ulcerative colitis in our sample collection. 相似文献
993.
Sun J Zheng SL Wiklund F Isaacs SD Purcell LD Gao Z Hsu FC Kim ST Liu W Zhu Y Stattin P Adami HO Wiley KE Dimitrov L Sun J Li T Turner AR Adams TS Adolfsson J Johansson JE Lowey J Trock BJ Partin AW Walsh PC Trent JM Duggan D Carpten J Chang BL Grönberg H Isaacs WB Xu J 《Nature genetics》2008,40(10):1153-1155
We carried out a fine-mapping study in the HNF1B gene at 17q12 in two study populations and identified a second locus associated with prostate cancer risk, approximately 26 kb centromeric to the first known locus (rs4430796); these loci are separated by a recombination hot spot. We confirmed the association with a SNP in the second locus (rs11649743) in five additional populations, with P = 1.7 x 10(-9) for an allelic test of the seven studies combined. The association at each SNP remained significant after adjustment for the other SNP. 相似文献
994.
Identification of ten loci associated with height highlights new biological pathways in human growth 总被引:1,自引:0,他引:1
Lettre G Jackson AU Gieger C Schumacher FR Berndt SI Sanna S Eyheramendy S Voight BF Butler JL Guiducci C Illig T Hackett R Heid IM Jacobs KB Lyssenko V Uda M;Diabetes Genetics Initiative;FUSION;KORA;Prostate Lung Colorectal Ovarian Cancer Screening Trial;Nurses' Health Study;SardiNIA Boehnke M Chanock SJ Groop LC Hu FB Isomaa B Kraft P Peltonen L Salomaa V Schlessinger D Hunter DJ Hayes RB Abecasis GR Wichmann HE Mohlke KL Hirschhorn JN 《Nature genetics》2008,40(5):584-591
Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet-undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in >10,000 subjects. Ten newly identified and two previously reported loci were strongly associated with variation in height (P values from 4 x 10(-7) to 8 x 10(-22)). Together, these 12 loci account for approximately 2% of the population variation in height. Individuals with < or =8 height-increasing alleles and > or =16 height-increasing alleles differ in height by approximately 3.5 cm. The newly identified loci, along with several additional loci with strongly suggestive associations, encompass both strong biological candidates and unexpected genes, and highlight several pathways (let-7 targets, chromatin remodeling proteins and Hedgehog signaling) as important regulators of human stature. These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait. 相似文献
995.
996.
健美操动作具有强烈的节奏性,是通过音乐充分地表现出来.因此音乐是健美操运动不可缺少的组成部分.音乐是健美操练习的口令,是运动的节拍,音乐对健美操练习起重要的支配作用.音乐的旋律、速度能使健美操练习更具有感染力.健美操运动之所以深受人们的喜爱,很重要的因素之一是现代音乐给健美操带来了活力. 相似文献
997.
Isolated islets from C57Bl/6J mice exposed to 10 mmoles/l glucose supplemented with 5 micrograms/ml glibenclamide for 48 h released significantly less insulin in the subsequent short-time incubation than untreated controls (without glibenclamide), whereas insulin biosynthesis was not suppressed by glibenclamide treatment. 相似文献
998.
Summary The röntgenokymographical measurement of the speed of flow of the blood is based on the observation that, with the Stumpf kymograph, progressive movements taking place longitudinally can be recorded with the same ease as periodically recurrent, sinusoid movements. From the time during which the kymograph operates, which can be read off the time relay, and a few measurable stretches of the kymogram defined in detail in the text, the speed of propagation of a directed process of movement can be calculated. If a drop of iodized oil traverses the vessel at the same speed as the blood, the speed of flow of the blood can be ascertained. In numerous tests on models not only was the practicability of the method as such proved, but more specialized conditions of flow in tubes of irregular lumen or having aneurysmal sacculations were examined. In this connection vortical formations are very clearly shown. The particular merit of this new röntgenokymographical method (flow kymography) is seen to reside in the fact that the cycle of speeds can be followed along a considerable length of vessel, and also that circumscribed alterations in speed within the part-sections examined can be anatomically localized. Experiments in the use of the method on human subjects are in preparation. 相似文献
999.
1000.