Gene-environment Interaction: Variability Gene Concept

Berg, Kåre

doi:10.1007/978-94-011-1130-0_26

Cited by 20 publications

(13 citation statements)

References 27 publications

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“…31 The findings from the present and previous studies provide supporting evidence for the concept of "variability genes," which may influence within-person variability in phenotypes over time through the gene-environment interactions. 37 It is well known that males generally have higher blood pressure levels and prevalence of hypertension than females. 15,38 A gender difference in genetic influence on blood pressure was found among male and female twins.…”

Section: Discussionmentioning

confidence: 99%

Gender-Specific Influence of NO Synthase Gene on Blood Pressure Since Childhood

Chen

Srinivasan

et al. 2004

Hypertension

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Abstract-Impaired endothelial function caused by decreased NO production plays a pathophysiologic role in essential hypertension. Although cross-sectional data are available on the association between endothelial NO synthase gene polymorphisms and hypertension, whether the gene variants and their haplotypes affect the long-term cumulative burden and trend of blood pressure since childhood is not known. This aspect was examined using 4 polymorphisms and a community-based longitudinal cohort of 347 blacks and 801 whites aged 18 to 45 years who have been examined serially 4 to 13 times (7705 observations) over an on average of 23.4 years. The area under the curve calculated using a growth curve of serial measurements of mean arterial pressure was used as a long-term cumulative burden. Blacks compared with whites displayed significantly lower frequencies of the rare alleles for G894T (0.112 versus 0.325), G10T (0.209 versus 0.323), T-786C (0.147 versus 0.372), and A-922G (0.131 versus 0.355). In addition, T-786C and A-922G polymorphisms were in complete linkage disequilibrium in both races. After adjusting for age and body mass index, the 894T and 10T alleles were significantly associated with lower long-term burden of blood pressure since childhood in black females and white females, respectively. With respect to haplotypes, the G894-10T carriers compared with (G894-G10)/(G894-G10) showed significantly lower long-term burden and trend of blood pressure in white females. In conclusion, the endothelial NO synthase gene influences the long-term burden and trend of blood pressure since childhood in females and may contribute to their predisposition to hypertension. The gene encoding endothelial NO synthase (eNOS), which has 26 exons and spans Ϸ22 kb of the genome, maps to chromosome 7q35-7q36. 5 In humans, several sequence variants in the promoter region, exons and introns, have been identified. 5,6 Of these variants, A-922G and T-786C are located in the promoter region: G894T in exon 7, and G10T in intron 23. Although the relationship between endothelial NO production and blood pressure has been studied extensively, information on the association of the eNOS gene variants and their haplotypes with blood pressure is limited and conflicting. [7][8][9][10][11][12][13] Moreover, association studies on the eNOS gene and blood pressure have been so far cross-sectional in nature.Blood pressure increases with age at different rates 14,15 and has a large variability over time, including inherent physiological fluctuations and measurement errors. 16 In addition to the levels at a specific time point, genes may affect the longitudinal trends of blood pressure determined by within-person variability. A substantial genetic contribution to changes in blood pressure over time has been demonstrated in longitudinal twin and family studies. 17,18 Further, using serial measurements of a trait at multiple time points dilutes the measurement errors and minimizes the short-term fluctuations. 19,20 This notion is supported by earlier findin...

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Section: Discussionmentioning

confidence: 99%

Gender-Specific Influence of NO Synthase Gene on Blood Pressure Since Childhood

Chen

Srinivasan

et al. 2004

Hypertension

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“…3,11 Influence of familial hypertension on blood pressure reactivity and BMI may be attributed to the concept of the variability gene and it could also be due to interactions between different genes directly influencing the regulation of blood pressure response to various physical and psychological stimuli. 12 Diastolic pressure and mean arterial pressure did not have significant difference, both in Mean+SD and p-value. But, it is contradictory to the findings reported by Syed et al, where significant difference was also observed for diastolic blood pressure and mean arterial pressure between off springs of hypertensive and normotensive parents.…”

Section: Discussionmentioning

confidence: 74%

Elevated blood pressure and obesity in young adults of hypertensive parent versus normotensive parent

Ramya

Mukundan

2016

Int J Res Med Sci

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“…The findings from the present and previous studies provide supporting evidence for the concept of "variability genes," which may influence within-person variability in phenotypes over time through the gene-environment interactions. 7 There is evidence for the role of ␣-adducin gene in blood pressure regulation and hypertension in animal studies and some human populations. 35 Suggestive linkage to DBP total AUC was noted in this study on chromosome 4p16 where the ␣-adducin gene is located.…”

Section: Chen Et Al Genetic Loci For Blood Pressure Since Childhood 957mentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

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

Chen

Srinivasan

et al. 2005

Hypertension

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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...

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Gene-environment Interaction: Variability Gene Concept

Cited by 20 publications

References 27 publications

Gender-Specific Influence of NO Synthase Gene on Blood Pressure Since Childhood

Gender-Specific Influence of NO Synthase Gene on Blood Pressure Since Childhood

Elevated blood pressure and obesity in young adults of hypertensive parent versus normotensive parent

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

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