Document Detail


KIF5B gene sequence variation and response of cardiac stroke volume to regular exercise.
MedLine Citation:
PMID:  18984674     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A genome-wide linkage scan for endurance training-induced changes in stroke volume detected a quantitative trait locus on chromosome 10p11 in white families of the HERITAGE Family Study. Dense microsatellite mapping narrowed down the linkage region to a 7 Mb area containing 16 known and 14 predicted genes. Association analyses with 90 single nucleotide polymorphisms (SNPs) provided suggestive evidence (P values from 0.03 to 0.06) for association in the kinesin heavy chain (KIF5B) gene locus in the whole cohort. The associations at the KIF5B locus were stronger (P values from 0.001 to 0.008) when the analyses were performed on linkage-informative families only (family-specific logarithm of the odds ratio scores >0.025 at peak linkage location). Resequencing the coding and regulatory regions of KIF5B revealed no new exonic SNPs. However, the putative promoter region was particularly polymorphic, containing eight SNPs with at least 5% minor allele frequency within 1850 bp upstream of the start codon. Functional analyses using promoter haplotype reporter constructs led to the identification of sequence variants that had significant effects on KIF5B promoter activity. Analogous inhibition and overexpression experiments showed that changes in KIF5B expression alter mitochondrial localization and biogenesis in a manner that could affect the ability of the heart to adjust to regular exercise. Our data suggest that KIF5B is a strong candidate gene for the response of stroke volume to regular exercise. Furthermore, training-induced changes in submaximal exercise stroke volume may be due to mitochondrial function and variation in KIF5B expression as determined by functional SNPs in its promoter.
Authors:
George Argyropoulos; Adrian M Stütz; Olha Ilnytska; Treva Rice; Margarita Teran-Garcia; D C Rao; Claude Bouchard; Tuomo Rankinen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-11-04
Journal Detail:
Title:  Physiological genomics     Volume:  36     ISSN:  1531-2267     ISO Abbreviation:  Physiol. Genomics     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-12     Completed Date:  2009-02-26     Revised Date:  2010-09-22    
Medline Journal Info:
Nlm Unique ID:  9815683     Medline TA:  Physiol Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  79-88     Citation Subset:  IM    
Affiliation:
Energy Balance Laboratory, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808-4124, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Cells, Cultured
Chromosomes, Human, Pair 11 / genetics
Cohort Studies
Female
Genetic Variation*
Genome, Human
Genotype
Humans
Kinesin / genetics*
Male
Mice
Microsatellite Repeats
Molecular Sequence Data
Myocardium / metabolism*
Physical Endurance / genetics*
Polymorphism, Single Nucleotide
Promoter Regions, Genetic
Stroke Volume / genetics*,  physiology
Transfection
Grant Support
ID/Acronym/Agency:
HL-45670/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/KIF5B protein, human; EC 3.6.1.-/Kinesin
Comments/Corrections

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