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- Vasan, Ramachandran S, et al.
(författare)
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Genetic variants associated with cardiac structure and function : a meta-analysis and replication of genome-wide association data
- 2009
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 302:2, s. 168-178
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. OBJECTIVE: To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. DESIGN, SETTING, AND PARTICIPANTS: Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n = 4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10(-7) to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort. MAIN OUTCOME MEASURES: Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size. RESULTS: In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1% of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance). CONCLUSIONS: We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease.
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- Lie, S. O., et al.
(författare)
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Long-term results in children with AML: NOPHO-AML Study Group--report of three consecutive trials
- 2005
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 19:12, s. 2090-100
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Tidskriftsartikel (refereegranskat)abstract
- In all, 447 children with acute myeloid leukaemia (AML) have been treated on three consecutive NOPHO studies from July 1984 to December 2001. NOPHO-AML 84 was of moderate intensity with an induction of three courses of cytarabine, 6-thioguanine and doxorubicin followed by four consolidation courses with high-dose cytarabine. The 5-year event-free survival (EFS), disease free survival (DFS) and overall survival (OS) were 29, 37 and 38%. NOPHO-AML 88 was of high intensity with the addition of etoposide and mitoxantrone in selected courses during induction and consolidation. The interval between the induction courses should be as short as possible, that is, time intensity was introduced. The 5-year EFS, DFS and OS were 41, 48 and 46%. In NOPHO-AML 93, the treatment was stratified according to response to first induction course. The protocol utilised the same induction blocks as NOPHO-AML 88, but after the first block, children with a hypoplastic, nonleukaemic bone marrow were allowed to recover before the second block. Consolidation was identical with NOPHO-AML 88. The 5-year EFS, DFS and OS in NOPHO-AML 93 were 48, 52 and 65%. The new NOPHO-AML protocol has been based on experiences from previous protocols with stratification of patients with regard to in vivo response and specific cytogenetic aberrations.
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- Zeller, B., et al.
(författare)
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Acute leukaemia in children with Down syndrome: a population-based Nordic study
- 2005
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Ingår i: Br J Haematol. - : Wiley. - 0007-1048 .- 1365-2141. ; 128:6, s. 797-804
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Tidskriftsartikel (refereegranskat)abstract
- To determine the epidemiology and outcome of children with Down syndrome (DS) diagnosed with acute leukaemia in the Nordic countries, data registered in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) population-based leukaemia registry were analysed. Of 3494 children with acute leukaemia diagnosed between July 1984 and December 2001, 136 patients (3.9%) with DS were identified. 2.1% of the children with acute lymphoid leukaemia (ALL) and 14.0% of the children with acute myeloid leukaemia (AML) had DS. In ALL, DS patients had similar age and sex distribution and no major differences in blood counts compared with non-DS children. None of the DS patients had T cell leukaemia. Outcome was inferior to that of non-DS children and treatment results did not improve over time. In AML, DS patients showed a significant female predominance and all but one were <5 years old. DS patients with AML had significantly lower platelet and white blood cell counts and two-thirds were type M7 as according to the French-American-British classification. None of the patients <5 years of age had typical AML cytogenetic aberrations. Outcome was far better in the DS group. DS patients treated for AML after 1992 had an excellent outcome (probability of event-free survival, 83 +/- 6%). The high proportion of female DS patients with AML is unexplained. The differing treatment results in AML versus ALL need further evaluation and represent a challenge for the coming years.
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- Zeller, B, et al.
(författare)
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Childhood idiopathic thrombocytopenic purpura in the Nordic countries: Epidemiology and predictors of chronic disease
- 2005
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Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 94:2, s. 178-184
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To describe the epidemiology of idiopathic thrombocytopenic purpura (ITP) in the Nordic countries, to define clinical subgroups and to investigate factors predicting chronic disease. Methods: A prospective registration was done from 1998 to 2000, including all children with newly diagnosed ITP aged 0-14 y and at least one platelet count <30 x 10(9)/l. Results: 506 children were registered and 423 followed for 6 mo. The incidence was 4.8/10(5) per year. Most children were aged 0-7 y (78%), with a predominance of boys, while patients aged 8-14 y had equal representation of the two sexes. There were seasonal variations determined by variations in postinfectious cases with sudden onset. The platelet count was <10x10(9)/l in 58%, but bleeding manifestations were mild or moderate in 97%. The insidious form (symptoms for more than 2 wk) was more frequent in older children and girls, showed little seasonal variation, had milder manifestations and ran a chronic course in more than half the cases. Intracranial haemorrhages did not occur in the first 6 mo after diagnosis. Chronic ITP developed in 25%. The strongest predictor of chronic disease was insidious onset of symptoms (OR 5.97). Conclusion: In the Nordic countries, ITP mainly affects children aged 0-7 y, with a winter bulk of postinfectious cases superimposed on a steady occurrence of non-infectious cases. Clinically, it may be useful to distinguish between children with sudden versus insidious onset of symptoms rather than between different age groups.
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