Journal ArticleDOI
A common haplotype and the Pro582Ser polymorphism of the hypoxia-inducible factor-1alpha (HIF1A) gene in elite endurance athletes.
Frank Döring,Simone Onur,Alexandra Fischer,Marcel R. Boulay,Louis Pérusse,Tuomo Rankinen,Rainer Rauramaa,Bernd Wolfarth,Claude Bouchard +8 more
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TLDR
Preliminary evidence is found that the Hif1A Pro582Ser polymorphism and a common haplotype of the HIF1A gene may be associated with EEA status in Caucasian men.Abstract:
Hypoxia-inducible factor-1alpha (HIF1A) is a transcription factor regulating several genes in response to hypoxic stimuli. HIF1A target genes code for proteins involved in oxygen transport, glycolytic enzymes, and glucose transporters. We investigated whether single-nucleotide polymorphisms and haplotypes in the HIF1A gene are associated with endurance performance in the Genathlete cohort, which includes 316 Caucasian male elite endurance athletes (EEA) with a maximal oxygen uptake of 79.0+/-3.5 ml.kg(-1).min(-1) (mean+/-SD) and 304 Caucasian male sedentary controls with a maximal oxygen uptake of 40.1+/-7.0 ml.kg(-1).min(-1). Six single-nucleotide polymorphisms (rs1951795, rs11158358, rs2301113, rs11549465, rs115494657, rs17099207) were genotyped with the TaqMan system. We found a nominal significant tendency for a difference between the two groups for HIF1A Pro582Ser (rs11549465) genotype distributions (Pchi2=0.017). Homozygotes of the Pro genotype were slightly more frequent in athletes than in controls (84 vs. 75%). Compared with Ser carriers, the odds ratio (OR) of being an EEA in Pro/Pro homozygotes was 1.77 [95% confidence interval (CI): 1.18-2.67, P=0.006] compared with the other genotypes. A common HIF1A haplotype (frequency: 15%), including the rs11549465 Pro allele and the minor A allele of rs17099207 in the 3' flanking region of the gene, showed a significant association with EEA status (OR: 2.37, 95% CI: 1.21-4.66, P=0.012), whereas the most prevalent haplotype (frequency: 59%) comprising the rs11549465 Pro allele and the major G allele of rs1709920 showed no association with EEA status (OR: 0.93, 95% CI: 0.58-1.50, P=0.769). We found preliminary evidence that the HIF1A Pro582Ser polymorphism and a common haplotype of the HIF1A gene may be associated with EEA status in Caucasian men.read more
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Journal ArticleDOI
The Great British Medalists Project: A Review of Current Knowledge on the Development of the World's Best Sporting Talent.
Tim Rees,Lew Hardy,Arne Güllich,Bruce Abernethy,Jean Côté,Tim Woodman,Hugh Montgomery,Stewart Laing,Chelsea Warr +8 more
TL;DR: This work addresses the challenge of avoiding adherence to any specific model or area and by providing a reasoned review across three key overarching topics: (a) the performer; (b) the environment; and (c) practice and training by reviewing and calibrating evidence by performance level of the samples.
Book ChapterDOI
Current Progress in Sports Genomics
TL;DR: Future research including multicenter GWAS, whole-genome sequencing, epigenetic, transcriptomic, proteomic, and metabolomic profiling and performing meta-analyses in large cohorts of athletes is needed before these findings can be extended to practice in sport.
Journal ArticleDOI
Genes and elite athletes: a roadmap for future research
TL;DR: The present review aims to introduce novel methodological approaches in the field of sports genetics research, which can be applied in the near future to analyse the genotype profile associated with elite athletic status, using genotype–phenotype association studies using gene expression analysis, analysis of post‐transcriptional factors, and novel algorithm approaches.
Journal ArticleDOI
Advances in exercise, fitness, and performance genomics in 2010.
James M. Hagberg,Tuomo Rankinen,Ruth J. F. Loos,Louis Pérusse,Stephen M. Roth,Bernd Wolfarth,Claude Bouchard +6 more
TL;DR: Evidence continues to be strong for a role of gene-exercise interaction effects on the improvement in insulin sensitivity after exposure to regular exercise.
Journal ArticleDOI
Hypoxia-inducible factors and diabetes.
TL;DR: The range of evidence implicating HIFs in β-cell dysfunction, diabetes pathogenesis, and diabetes complications is discussed, and the differing outcomes of HIF-targeting approaches in these conditions are examined.
References
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Journal ArticleDOI
C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation.
Andrew C. R Epstein,Jonathan M. Gleadle,Luke A. McNeill,Kirsty S. Hewitson,J F O'Rourke,David R. Mole,Mridul Mukherji,Eric Metzen,Michael A Wilson,Anu Dhanda,Ya-Min Tian,Norma Masson,Donald L. Hamilton,Panu Jaakkola,Robert Barstead,Jonathan Hodgkin,Patrick H. Maxwell,Christopher W. Pugh,Christopher J. Schofield,Peter J. Ratcliffe +19 more
TL;DR: Direct modulation of recombinant enzyme activity by graded hypoxia, iron chelation, and cobaltous ions mirrors the characteristics of HIF induction in vivo, fulfilling requirements for these enzymes being oxygen sensors that regulate HIF.
Journal ArticleDOI
Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population.
TL;DR: An expectation-maximization (EM) algorithm leading to maximum-likelihood estimates of molecular haplotype frequencies under the assumption of Hardy-Weinberg proportions is implemented and appears to be useful for the analysis of nuclear DNA sequences or highly variable loci.
Journal ArticleDOI
Signal transduction to hypoxia-inducible factor 1.
TL;DR: In human cancer cells, both intratumoral hypoxia and genetic alterations affecting signal transduction pathways lead to increased HIF-1 activity, which promotes angiogenesis, metabolic adaptation, and other critical aspects of tumor progression.
Journal ArticleDOI
The human gene map for performance and health-related fitness phenotypes: the 2005 update.
Molly S. Bray,James M. Hagberg,Louis Pérusse,Tuomo Rankinen,Stephen M. Roth,Bernd Wolfarth,Claude Bouchard +6 more
TL;DR: This review presents the 2002 update of the human gene map for physical performance and health-related phenotypes, based on peer-reviewed papers published by the end of 2002 and includes association studies with candidate genes, genome-wide scans with polymorphic markers, and single gene defects causing exercise intolerance to variable degrees.
Journal ArticleDOI
Testing association of statistically inferred haplotypes with discrete and continuous traits in samples of unrelated individuals.
Dmitri V. Zaykin,Peter H. Westfall,S. Stanley Young,Maha A Karnoub,Michael J. Wagner,Margaret G. Ehm +5 more
TL;DR: Analysis of real data comprised of a dense map of single nucleotide polymorphisms spaced along a 12-cM chromosomal region allows us to confirm the utility of the haplotype approach as well as the validity and usefulness of the proposed statistical technique.