Genomic Scan for Exercise Blood Pressure in the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study

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Abstract
A genome-wide linkage scan was performed for genes affecting submaximal exercise systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the sedentary state and their responses to a standardized endurance training program. A total of 344 polymorphic markers were used, and 344 pairs of siblings from 99 white nuclear families and 102 sibling pairs from 105 black family units were available for the study. All subjects were healthy but sedentary at baseline. SBP and DBP were measured during exercise tests at 2 different intensities: 50 W (SBP50 and DBP50) and 80% of maximal oxygen consumption (SBP80 and DBP80). Baseline blood pressure phenotypes were adjusted for age, gender, and body mass index, and the training responses (after training minus baseline [Δ]) were adjusted for age, gender, baseline body mass index, and baseline blood pressure. Two analytical strategies were used: a multipoint variance-components linkage analysis using all the family data and a single-point linkage analysis using pairs of siblings. In whites, promising linkages (lod score >1.75) were detected for baseline SBP80 on 10q23-q24 and for ΔSBP50 on 8q21. In addition, several chromosomal regions with suggestive evidence of linkage (lod score 1.0 to 1.75) were observed for SBP50 (22q11.2-q13), DBP50 (6q23-q27), SBP80 (2p24, 2q21, 14q11.1-q12, and 16q21), DBP80 (6q13-q21), ΔSBP50 (7p12-p13), and ΔDBP50 (5q31-q32). In blacks, DBP50, DBP80, and ΔDBP80 showed promising quantitative trait loci on 18p11.2, 11q13-q21, and 10q21-q23, respectively. Suggestive linkages were evident for DBP50 on 2p22-p25, 11p15.5, and 18q21.1; for SBP80 on 6q21-q21, 6q31-q36, 12q12-q13, 15q12-q13, and 17q11-q12; and for DBP80 on 8q24, 10q21-q24, and 12p13. All the detected chromosomal regions include several potential candidate genes and therefore warrant further studies in the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) cohort and other studies.