HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 15/1/27    most recent 00147.2002v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Rankinen, T. Articles by Bouchard, C. Search for Related Content PubMed PubMed Citation Articles by Rankinen, T. Articles by Bouchard, C.

Titin is a candidate gene for stroke volume response to endurance training: the HERITAGE Family Study

¹ Pennington Biomedical Research Center, Human Genomics Laboratory, Baton Rouge, Louisiana 70808
² Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri 63110
³ School of Kinesiology and Leisure Studies, University of Minnesota, Minneapolis, Minnesota 55455
⁴ Department of Kinesiology, Indiana University, Bloomington, Indiana 46405
⁵ Department of Health and Kinesiology, Texas A & M University, College Station, Texas 77843-4243
⁶ Departments of Genetics and Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110-1093

A genome-wide linkage scan for endurance training-induced changes in submaximal exercise stroke volume (SV50) in the HERITAGE Family Study revealed two chromosomal regions (2q31–q32 and 10p11.2) with at least suggestive evidence of linkage among white families. Here we report a further characterization of the quantitative trait locus (QTL) in chromosome 2q31 and provide evidence that titin (TTN) is likely a candidate gene involved. The original linkage was detected with two markers (D2S335 and D2S1391), and the QTL covered 25 million base pairs (Mb). We added 12 microsatellite markers resulting in an average marker density of one marker per 2.3 Mb. The evidence of linkage increased from P = 0.006 to P = 0.0002 and 0.00002 in the multi- and single-point analyses, respectively. The strongest evidence of linkage was seen with two markers in and near the TTN gene. Transmission/disequilibrium test (TDT) with the same marker set provided evidence for association with one of the TTN markers (D2S385; P = 0.004). TTN is a major contributor to the elasticity of cardiomyocytes and a key regulator of the Frank-Starling mechanism. Since TTN is the largest gene in the human genome, the challenge is to identify the DNA sequence variants contributing to the interindividual differences in cardiac adaptation to endurance training.

genetics; fine mapping; exercise training; cardiac function; linkage; association studies

This article has been cited by other articles:

				W. Yang, T. Kelly, and J. He Genetic Epidemiology of Obesity Epidemiol. Rev., June 12, 2007; (2007) mxm004v1. [Abstract] [Full Text] [PDF]