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Sökning: WFRF:(Rankinen Tuomo) > (2010-2014) > Using molecular cla...

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FältnamnIndikatorerMetadata
00005338naa a2200613 4500
001oai:DiVA.org:su-48910
003SwePub
008101210s2010 | |||||||||||000 ||eng|
009oai:prod.swepub.kib.ki.se:120932822
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-489102 URI
0247 a https://doi.org/10.1152/japplphysiol.01295.20092 DOI
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:1209328222 URI
040 a (SwePub)sud (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Timmons, James A.u Stockholms universitet,Wenner-Grens institut4 aut
2451 0a Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans
264 1b American Physiological Society,c 2010
338 a print2 rdacarrier
500 a authorCount :21
520 a Timmons JA, Knudsen S, Rankinen T, Koch LG, Sarzynski M, Jensen T, Keller P, Scheele C, Vollaard NB, Nielsen S, Akerstrom T, MacDougald OA, Jansson E, Greenhaff PL, Tarnopolsky MA, van Loon LJ, Pedersen BK, Sundberg CJ, Wahlestedt C, Britton SL, Bouchard C. Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans. J Appl Physiol 108: 1487-1496, 2010. First published February 4, 2010; doi:10.1152/japplphysiol.01295.2009.-A low maximal oxygen consumption ((V) over dotO(2max)) is a strong risk factor for premature mortality. Supervised endurance exercise training increases (V) over dotO(2max) with a very wide range of effectiveness in humans. Discovering the DNA variants that contribute to this heterogeneity typically requires substantial sample sizes. In the present study, we first use RNA expression profiling to produce a molecular classifier that predicts (V) over dotO(2max) training response. We then hypothesized that the classifier genes would harbor DNA variants that contributed to the heterogeneous (V) over dotO(2max) response. Two independent preintervention RNA expression data sets were generated (n = 41 gene chips) from subjects that underwent supervised endurance training: one identified and the second blindly validated an RNA expression signature that predicted change in (V) over dotO(2max) (""predictor"" genes). The HERITAGE Family Study (n = 473) was used for genotyping. We discovered a 29-RNA signature that predicted (V) over dotO(2max) training response on a continuous scale; these genes contained similar to 6 new single-nucleotide polymorphisms associated with gains in (V) over dotO(2max) in the HERITAGE Family Study. Three of four novel candidate genes from the HERITAGE Family Study were confirmed as RNA predictor genes (i.e., ""reciprocal"" RNA validation of a quantitative trait locus genotype), enhancing the performance of the 29-RNA-based predictor. Notably, RNA abundance for the predictor genes was unchanged by exercise training, supporting the idea that expression was preset by genetic variation. Regression analysis yielded a model where 11 single-nucleotide polymorphisms explained 23% of the variance in gains in (V) over dotO(2max), corresponding to similar to 50% of the estimated genetic variance for (V) over dotO(2max). In conclusion, combining RNA profiling with single-gene DNA marker association analysis yields a strongly validated molecular predictor with meaningful explanatory power. (V) over dotO(2max) responses to endurance training can be predicted by measuring a similar to 30-gene RNA expression signature in muscle prior to training. The general approach taken could accelerate the discovery of genetic biomarkers, sufficiently discrete for diagnostic purposes, for a range of physiological and pharmacological phenotypes in humans.
653 a endurance training
653 a genotype
653 a personalized medicine
653 a NATURAL SCIENCES
653 a NATURVETENSKAP
7001 a Knudsen, Steen4 aut
7001 a Rankinen, Tuomo4 aut
7001 a Koch, Lauren G.4 aut
7001 a Sarzynski, Mark4 aut
7001 a Jensen, Thomas4 aut
7001 a Keller, Pernille4 aut
7001 a Scheele, Camillau Stockholms universitet,Wenner-Grens institut4 aut
7001 a Vollaard, Niels B. J.4 aut
7001 a Nielsen, Soren4 aut
7001 a Akerstrom, Thorbjoern4 aut
7001 a MacDougald, Ormond A.4 aut
7001 a Jansson, Evau Karolinska Institutet4 aut
7001 a Greenhaff, Paul L.4 aut
7001 a Tarnopolsky, Mark A.4 aut
7001 a van Loon, Luc J. C.4 aut
7001 a Pedersen, Bente K.4 aut
7001 a Sundberg, Carl Johanu Karolinska Institutet4 aut
7001 a Wahlestedt, Claes4 aut
7001 a Britton, Steven L.4 aut
7001 a Bouchard, Claude4 aut
7102 a Stockholms universitetb Wenner-Grens institut4 org
7730 t Journal of applied physiologyd : American Physiological Societyg 108:6, s. 1487-1496q 108:6<1487-1496x 8750-7587x 1522-1601
8564 u https://europepmc.org/articles/pmc2886694
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-48910
8564 8u https://doi.org/10.1152/japplphysiol.01295.2009
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:120932822

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