Autosomal Genome Scan for Loci Linked to Blood Pressure Levels and Trends Since Childhood

Abstract

Abstract-Genetic loci influencing the long-term levels and trends of blood pressure over time were investigated using 775 white siblings, ages 13 to 43 years, enrolled in the Bogalusa Heart Study, and 357 microsatellite markers on the 22 autosomal chromosomes. Subjects had been examined serially 2 to 12 times with 4365 serial observations over an average of 22 years from childhood to adulthood. Total and incremental area under the curve was calculated based on a cubic growth curve and used as long-term levels and trends, respectively. After adjusting for age, sex, and body mass index, heritability estimates of total area were 0.66 for systolic and 0.68 for diastolic blood pressure. Heritability of incremental area was 0.38 for systolic and 0.46 for diastolic blood pressure. Significant linkage to the total area of diastolic blood pressure (peak logarithm of odds [LOD]ϭ3.9 at 73 cM) was observed on chromosome 2, with a region spanning from 44 cM to 103 cM showing supporting linkage evidence of LOD Ͼ3.0. In addition, suggestive linkage for total area of systolic (LODϭ1.6 at 182 cM) and diastolic blood pressure (LODϭ2.0 at 36 cM) on chromosome 4 and diastolic blood pressure incremental area (LODϭ2.2 at 28 cM) on chromosome 18 was noted. Several hypertension candidate genes such as ␣-adducin, ␤-adducin, sodium bicarbonate co-transporter, and G protein-coupled receptor kinase 4 are located in these regions. Linkage evidence found in this community-based study indicates that regions on these chromosomes harbor genetic loci that affect the propensity for development of hypertension from childhood. Key Words: blood pressure E ssential hypertension is a polygenic disorder that results from the interplay of multiple susceptibility genes and environmental factors. 1 Numerous genome-wide linkage studies to localize genes influencing blood pressure and hypertension status in a number of populations and ethnic groups have found linkage evidence in regions on multiple chromosomes. 2 However, most linkage studies on blood pressure and hypertension have thus far been cross-sectional in nature, representing between-person variability at a specific time point only.Blood pressure increases with age at different rates. 3,4 In addition to levels, genes may also affect the longitudinal trends of blood pressure that represent within-person variability. A substantial genetic contribution to the changes in blood pressure over time has been demonstrated in longitudinal twin and family studies. 5,6 A concept of "variability genes," whose expression depends on environmental exposure, is proposed to explain the within-person variability. 7 Further, using serial measurements of a trait at multiple time points dilutes the measurement errors and minimizes the short-term influences when the trait is subject to variation from time to time within the same individual. 8,9 This notion is supported by earlier findings from studies on genetics and epidemiology of blood pressure. 10,11 Therefore, measures of long-term levels and trend of blood pressure...

Blood Pressure and Renal Sodium Handling in Relation to Genetic Variation in the DRD1 Promoter and GRK4

“…1 The genes encoding DRD1 and GRK4 localize to chromosomes 5q35.1 3 and 4p16.3, 4 respectively. The GRK4 gene locus is embedded in a cluster on chromosome 4p16, which is associated with hypertension 5,6 and also includes ␣-adducin (ADD1). To our knowledge, there are no studies showing significant genome-wide linkage of hypertension with the DRD1 locus, although a genome-scan meta-analysis 7 identified 5q as a suggestive region.…”

Genome-Wide Scan for Premature Hypertension Supports Linkage to Chromosome 2 in a Large Kyrgyz Family

“…22 The Bogalusa Heart Study showed significant evidence of linkage to 2p13 at 73 cM for longterm (child to young adult) levels of diastolic bp. 23 Additionally, a 140 to 170 cM interval has been linked to preeclampsia in Finnish 24 and Australasian 25 populations, whereas linkage peaks at 40 to 140 cM and at 230 cM, obtained with 2 independent Family Blood Pressure Program (FBPP) Studies, 26,27 immediately flank that of the candidate interval (155 to 233 cM) suggested by analysis of the Kyrgyz pedigree in this study.…”

The impact of regular long term physical load on cardiovascular functional parameters in children and adolescent athletes

“…Rowing includes the components of endurance and resistance training, but there is an upper and lower body imbalance that could influence to systolic blood pressure (16,17). On the other hand, this study cannot reject the possibility genetic predisposition to higher blood pressure during exercise (18,19).…”