Biomedical subjects

C F Sing

Publications and source records attributed to C F Sing.

At least 37 records · Page 2Linked to original sources

PubMed1999

The relationship between risk factor levels and presence of coronary artery calcification is dependent on apolipoprotein E genotype.

An important research question in the study of the genetics of coronary artery disease (CAD) is whether information about genetic variation will improve our ability to predict CAD beyond established risk factors. This question is especially relevant to the goal of identifying young, asymptomatic adults with coronary atherosclerosis who would benefit most from interventions to reduce risk. Coronary artery calcification (CAC) detected by electron-beam computed tomography is a relatively new method for detecting coronary atherosclerosis in asymptomatic individuals that has been shown to be a more accurate indicator of coronary atherosclerosis in asymptomatic individuals than other noninvasive techniques. In a study of asymptomatic women (n=169) and men (n=160) between the ages of 20 and 59 representative of the Rochester, Minnesota population, we used logistic regression to ask whether the most common Apolipoprotein (Apo) E genotypes (epsilon3/2, epsilon3/3, and epsilon4/3) predict the presence of CAC. The addition of information about ApoE genotypes to logistic models containing each separate risk factor did not improve prediction of CAC (P>0.10 in both women and men). However, there was significant evidence (P<0.10) that associations between variation in the probability of having CAC and variation in body mass index, plasma total cholesterol, and plasma ApoB in men and body mass index, plasma triglycerides, plasma ApoA1, and plasma ApoE in women were dependent on ApoE genotype. Thus, variation in the gene coding for ApoE may play a role in determining the contribution of established risk factors to risk of CAC.

Adult↗

PubMed1999

Context-dependent associations of the ACE I/D polymorphism with blood pressure.

The objective of the present study was to assess whether the influences of gender, age, or measures of body size on blood pressure are homogeneous among genotypes of the insertion/deletion (I/D) polymorphism of the gene that codes for angiotensin-converting enzyme (ACE). We studied a sample of 1875 non-Hispanic white individuals (988 female and 887 male subjects) between 5 and 90 years of age from the general population of Rochester, Minn. When statistical interactions between effects associated with the I/D polymorphism and age, height, and weight were not considered, there was no evidence of a significant relationship between variation in blood pressure level or diagnostic category (hypertension versus normotension) and variation in ACE genotype in either gender. However, in females 5 to 29.9 years of age, the linear regression relationships of systolic blood pressure level with age and weight and of diastolic blood pressure level with age were significantly heterogeneous among ACE genotypes. For these concomitant traits, the rank order of expected blood pressure levels associated with each genotype reversed from low values of the concomitant, in which blood pressure was lower for I/D heterozygotes than for II or DD homozygous, to high levels of the concomitant, in which blood pressure was higher for I/D heterozygotes than for II or DD homozygotes. In male subjects 50 to 90 years of age, the logistic regression relationship of the probability of having hypertension with height was also heterogeneous among ACE genotypes; it was statistically significant in II homozygotes but not statistically significant in either I/D heterozygotes or DD homozygotes. Findings of this study are consistent with the conclusion that the influence of variation in the ACE gene on interindividual variation in blood pressure is dependent on contexts that are indexed by gender, age, and measures of body size.

Adolescent↗

PubMed1998

Variation in the region of the angiotensin-converting enzyme gene influences interindividual differences in blood pressure levels in young white males.

BACKGROUND: The renin-angiotensin system regulates blood pressure through its effects on vascular tone, renal hemodynamics, and renal sodium and fluid balance. METHODS AND RESULTS: Using data from a large population-based sample of 1488 siblings having a mean age of 14.8 years and belonging to the youngest generation of 583 randomly ascertained three-generation pedigrees from Rochester, Minn, we carried out variance components-based linkage analyses to evaluate the contribution of variation in four renin-angiotensin system gene regions (angiotensinogen, renin, angiotensin I-converting enzyme, and angiotensin II receptor type 1) to interindividual variation in systolic, diastolic, and mean arterial pressure. We rejected the null hypothesis that allelic variation in the region of the angiotensin-converting enzyme (ACE) gene does not contribute to interindividual blood pressure variability. After conditioning on measured covariates, variation in this region accounted for 0%, 13% (P=0.04), and 16% (P=0.04) of the interindividual variance in systolic, diastolic, and mean arterial pressures, respectively. These estimates were even greater in a subset of subjects with a positive family history of hypertension (0%, 29% [P=0.005], and 32% [P<0.005], respectively). In sex-specific analyses, genetic variation in the region of the ACE gene significantly influenced interindividual blood pressure variation in males (37% for SBP [P=0.03], 38% for DBP [P=0.04], and 53% for MAP [P<0.005]) but not in females. CONCLUSIONS: Although it is possible that variation in a gene near the ACE gene may explain the observed results, knowledge about the physiological involvement of ACE in blood pressure regulation supports the proposition that the ACE gene itself influences blood pressure variability in a sex-specific manner.

Adolescent↗

PubMed1998

An ecological study of association between coronary heart disease mortality rates in men and the relative frequencies of common allelic variations in the gene coding for apolipoprotein E.

Three common alleles, epsilon2, epsilon3, and epsilon4, of the gene coding for apolipoprotein E (apoE) have been identified as predictors of interindividual variation in measures of lipid and lipoprotein metabolism, and ultimately risk of coronary heart disease (CHD), within many populations. Here we evaluated the utility of the geographic distribution of these alleles for prediction of interpopulation variation in average level of serum total cholesterol and other traditional risk factors, and CHD mortality rate. We employed published estimates of the relative frequencies of the three common apoE alleles, average levels of risk factors such as serum total cholesterol, systolic and diastolic blood pressure, body mass index, smoking prevalence and CHD mortality rate for nine population-based samples of middle-aged males studied by the international WHO MONICA Project. There was approximately a 10-fold difference between the highest and lowest CHD mortality rate. Of the traditional risk factors, variation in the average level of serum total cholesterol was the best predictor (approximately 33%) of the observed interpopulation variation in estimates of CHD mortality rate (Pr=0.10). Variation in the relative frequency of the epsilon4 allele predicted approximately 50% of interpopulation variation in average serum total cholesterol level (Pr=0.02) and 75% of the variation in CHD mortality rate (Pr=0.002) when information about variation in the other risk factors and the epsilon2 and epsilon3 alleles is ignored. Furthermore, variation in the relative frequency of the epsilon4 allele predicted approximately 40% of the variation in CHD mortality rate (Pr=0.02) after considering the contribution of variation in average serum total cholesterol level. Average serum total cholesterol level was estimated to increase by 0.114 mmol/l (4.405 mg/dl), and CHD mortality rate by 24.5/100000, for an increase of 0.01 in the relative frequency of the epsilon4 allele. The predictive utility of the epsilon2 and epsilon3 alleles was considerably less than that of the epsilon4 allele. For the sample of populations considered, the geographic distribution of the apoE alleles can be a statistically significant predictor of interpopulation variation in both the average serum total cholesterol level and CHD mortality rate. In particular, the epsilon4 allele may confer valuable ecological risk information.

Alleles↗

PubMed1998

Genetic structure of five susceptibility gene regions for coronary artery disease: disequilibria within and among regions.

We analyzed two-locus disequilibria for 16 polymorphic loci of seven susceptibility genes for coronary artery disease located in five chromosomal regions distributed across four chromosomes. Included were the genes coding for apolipoprotein B (ApoB, chromosome 2, four marker loci), lipoprotein lipase (LPL, chromosome 8, three marker loci), apolipoproteins AI, CIII AIV (ApoAI-CIII-AIV, chromosome 11, three marker loci), apolipoprotein E (ApoE, chromosome 19, two marker loci), and the low density lipoprotein receptor (LDLR, chromosome 19, four marker loci). Our sample included 540 unrelated individuals from the Rochester, Minn. population. There were no statistically significant deviations of single-locus genotypes from Hardy-Weinberg equilibrium. The strongest associations within genes were for composite diallelic disequilibria; 17/19 were significant (13 at Pr <0.001, 1 at Pr <0.01, 3 at Pr <0.05). These observations suggest marker alleles within genes have a shared evolutionary history reflected by disequilibria that have not been dissipated by recombination. Disequilibrium was not generally concordant with the physical orderings of markers. Only two significant higher-order disequilibria were observed although 12 triallelic disequilibria were at maximum possible values. We observed 19 statistically significant disequilibria (Pr <0.05; 4 composite diallelic, 13 triallelic, and 2 quadriallelic) between 101 pairs of marker loci, where each locus in a pair was from a different unlinked region. These unexpected results are most likely explained by recent historical factors, including worldwide population expansion and amalgamation with continuous admixture, that influence the genetic structure (organization of alleles and non-alleles into genotypes) of a population. We conclude that disequilibria between loci from unlinked regions may be more extensive than is commonly assumed. Our findings also suggest that it is, on average, at least 15 times more likely to not detect significant disequilibrium among unlinked loci when it is really present than to make a false positive inference. Disequilibria between functional loci within or between regions will impact estimates of genetic variance associated with particular functional mutations within a susceptibility gene region.

Apolipoproteins↗

PubMed1998

Correlates of family history of coronary artery disease in children.

The atherosclerotic process begins in childhood but, in general, does not reach the clinical horizon until after the fifth decade of life, at which point the best opportunities for prevention and intervention have been lost. In order to identify children with a high risk of developing coronary artery disease (CAD), risk factors measured in children that are the most informative indicators of future risk must be identified. Using a novel analytical strategy that incorporates a continuum of information about context dependency, we investigated whether there were significant differences in intermediate biochemical and physiological traits between children (189 females and 188 males, ages 5-20.5 years) with and without a strong family history of clinically-defined CAD at three levels of context dependency (coarse grain, medium grain, and fine grain). In the coarse-grained analysis we tested for differences in mean levels of nine intermediate traits (lipids, apolipoproteins, blood pressure traits) and indices of external and internal environmental context (age, body mass index, smoking status). Female children with a strong family history had higher average levels for total cholesterol, triglyceride, Apo B, and systolic blood pressure and were on average older and weighed more than female children with a weak family history of CAD. Male children with a strong family history of CAD had higher average levels of triglycerides and were on average older than male children with a weak family history. In the medium-grained analysis we investigated whether the regression relationships between each intermediate trait and each measure of environmental context was significantly different between children with and without a strong family history of CAD. Our results indicate that children with a strong family history of CAD have a significantly different relationship between their intermediate traits and environmental contexts than children with a weak family history. In the fine-grained analysis, we stratified the sample into age, BMI, and smoking subgroups and tested for mean differences in the intermediate traits between children with and without a strong family history. For seven of the nine intermediate traits we found evidence of significant mean differences between children with and without a strong family history of CAD in particular age and BMI subgroups in nonsmokers that were not expected given the results from separate age-dependent or BMI-dependent marginal analyses. From these analyses, we conclude that the inferences about intermediate biochemical and physiological trait associations with family history of CAD depend on where on the coarse-grain to fine-grain continuum of context dependency the analysis is performed. In many cases, inferences at one level of investigation are different than the inferences made at a coarser or finer level. This study documents the complexity of the associations between intermediate traits and risk of CAD and raises the question of how many models are needed to maximize disease prediction and where these models should fall on the coarse- to fine-grain continuum.

Adolescent↗

PubMed1998

DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene.

Lipoprotein lipase plays a central role in lipid metabolism and the gene that encodes this enzyme (LPL) is a candidate susceptibility gene for cardiovascular disease. Here we report the complete sequence of a fraction of the LPL gene for 71 individuals (142 chromosomes) from three populations that may have different histories affecting the organization of the sequence variation. Eighty-eight sites in this 9.7 kb vary among individuals from these three populations. Of these, 79 were single nucleotide substitutions and 9 sites involved insertion-deletion variations. The average nucleotide diversity across the region was 0.2% (or on average 1 variable site every 500 bp). At 34 of these sites, the variation was found in only one of the populations, reflecting the differing population and mutational histories. If LPL is a typical human gene, the pattern of sequence variation that exists in introns as well as exons, even for the small number of samples considered here, will present challenges for the identification of sites, or combinations of sites, that influence variation in risk of disease in the population at large.

Base Sequence↗

PubMed1998

Haplotype structure and population genetic inferences from nucleotide-sequence variation in human lipoprotein lipase.

Allelic variation in 9.7 kb of genomic DNA sequence from the human lipoprotein lipase gene (LPL) was scored in 71 healthy individuals (142 chromosomes) from three populations: African Americans (24) from Jackson, MS; Finns (24) from North Karelia, Finland; and non-Hispanic Whites (23) from Rochester, MN. The sequences had a total of 88 variable sites, with a nucleotide diversity (site-specific heterozygosity) of .002+/-.001 across this 9.7-kb region. The frequency spectrum of nucleotide variation exhibited a slight excess of heterozygosity, but, in general, the data fit expectations of the infinite-sites model of mutation and genetic drift. Allele-specific PCR helped resolve linkage phases, and a total of 88 distinct haplotypes were identified. For 1,410 (64%) of the 2,211 site pairs, all four possible gametes were present in these haplotypes, reflecting a rich history of past recombination. Despite the strong evidence for recombination, extensive linkage disequilibrium was observed. The number of haplotypes generally is much greater than the number expected under the infinite-sites model, but there was sufficient multisite linkage disequilibrium to reveal two major clades, which appear to be very old. Variation in this region of LPL may depart from the variation expected under a simple, neutral model, owing to complex historical patterns of population founding, drift, selection, and recombination. These data suggest that the design and interpretation of disease-association studies may not be as straightforward as often is assumed.

Animals↗

PubMed1998

Linkage and association of adrenergic and dopamine receptor genes in the distal portion of the long arm of chromosome 5 with systolic blood pressure variation.

Elevated blood pressure is an important risk factor for renal-, cerebro- and cardiovascular diseases. We used an efficient discordant sib-pair ascertainment scheme to investigate the impact of the distal end of the long arm of human chromosome 5 (chromosomal region 5q31.1-qter) containing genes for the alpha1B and beta2 adrenergic receptors and the dopamine receptor type 1A on variation of systolic blood pressure in young Caucasians. We measured eight highly polymorphic markers spanning this positional candidate gene-rich region in 427 individuals from 55 three-generation pedigrees containing 69 discordant sibling pairs, and calculated multipoint identity by descent (MIBD) probabilities. The results of genetic linkage and association tests indicate that the region between markers D5S2093 and D5S462 is significantly linked to one or more polymorphic genes influencing interindividual variation in systolic blood pressure levels. Since the alpha1B adrenergic receptor and dopamine receptor type 1A genes are located close to these markers, these data suggest that genetic variation in one or both of these G protein-coupled receptors, which participate in the control of vascular tone, plays an important role in influencing interindividual variation in systolic blood pressure levels.

Adolescent↗

PubMed1997

Association between common alleles of the low-density lipoprotein receptor gene region and interindividual variation in plasma lipid and apolipoprotein levels in a population-based sample from Rochester, Minnesota.

This paper presents an analysis of the relationship between variation in the low-density lipoprotein receptor (LDLR) gene region and interindividual variation in plasma lipid and apolipoprotein levels in a sample representative of the adult population of Rochester, Minn. (217 females and 187 males aged 26 to 63). This relationship was analyzed by estimating the average excesses of alleles of the LDLR gene defined using RFLP markers both singly and simultaneously. We also used a cladistic approach to illustrate the consequences of incorporating evolutionary information into the analysis of genotype-phenotype relationships. Although results from both approaches supported the inference that common variation in the LDLR gene region associates with small effects on plasma lipid and apolipoprotein levels, only the cladistic approach provides direction for further work aimed at identifying the functional DNA sequence variations responsible for the observed associations.

Adult↗

PubMed1997

A biometrical study of the relationship between sodium-lithium countertransport and triglycerides.

We addressed the question: Is there evidence that allelic variation in a single unmeasured gene that has a large effect on maximal activity of erythrocyte sodium-lithium countertransport (Na-Li CNT) also has pleiotropic effects on variation in plasma triglyceride levels? Complex segregation analysis models that included plasma triglyceride levels as a covariate were considered as explanations for interindividual variation in Na-Li CNT. A sample of 711 healthy adults from 254 pedigrees enrolled in the Rochester Family Heart Study was selected for this study. The majority of the pedigrees supported the hypothesis that variations in a single unmeasured non-transmitted environmental factor have large effects on the Na-Li CNT distribution. Only gender-specific first-order covariate parameters were necessary in the complex segregation models suggesting that the form of the relationship between Na-Li CNT and plasma triglyceride level was not influenced by variation in the inferred environmental factor with large effects. Stratification of the sample by this inferred environmental factor resulted in three classes of individuals with significant differences in the distributions of coronary heart disease risk factor traits, as well as interindividual variation in both Na-Li CNT and plasma triglyceride levels. These results, along with other observations from the Rochester Family Heart Study sample, emphasize the complex and multifactorial nature of the causes of interindividual variation in Na-Li CNT. Our study further suggests that new research strategies are needed for studying the relationships between genetic and environmental variation and variation in quantitative traits such as Na-Li CNT that have been identified as risk factors for hypertension.

Adult↗

PubMed1997

The response of renal plasma flow to angiotensin II infusion in a population-based sample and its association with the parental history of essential hypertension.

BACKGROUND: Results from previous studies suggested that a blunted response of renal plasma flow (RPF) to angiotensin II infusion during a high-sodium diet (a phenotype associated with nonmodulation) is an intermediate phenotype for essential hypertension. OBJECTIVE: To determine whether RPF traits used to investigate nonmodulation have the characteristics of intermediate traits when examined in a population-based sample of adults aged 20-49.9 years. DESIGN AND METHODS: We examined the frequency distribution of baseline RPF and of its response to All infusion using maximum-likelihood commingling analysis in order to investigate the null hypothesis that the distributions of these traits are unimodal. We also examined the null hypothesis that there is no association between these candidate intermediate traits and the parental history of essential hypertension. RESULTS: There was some evidence for the commingling of multiple distributions underlying these traits both for women and for men but the commingled distributions overlapped substantially and the inferences about the commingling of distributions were sensitive to the method of RPF measurement, exclusion of outliers, and the method of adjustment for concomitants. There was no statistically significant association between any of the RPF traits and a parental history of essential hypertension. CONCLUSIONS: There is not sufficiently strong evidence to advocate the use of this set of intermediate traits to identify high-risk individuals or to relate genetic variation to the variation in risk of essential hypertension within this age range in the population at large.

Adult↗

PubMed1997

The role of the apolipoprotein E polymorphism in the prediction of coronary artery disease age of onset.

We investigated the role of the apolipoprotein (Apo) E polymorphism in the prediction of CAD age of onset in a sample of unrelated living male (n = 65) and female (n = 54) Caucasian subjects diagnosed with CAD. Cumulative distributions of age at the first diagnosis of CAD were estimated for each Apo E genotype and tested for homogeneity using the log-rank test. The Apo epsilon 33 genotype was used as a reference group for all hypothesis tests. Analyses were performed separately in males and females. We found evidence suggesting that the presence of the Apo epsilon 32 genotype in males is associated with a significantly earlier CAD age of onset. These results suggest that the Apo E polymorphism may be a gender-specific predictor of CAD age of onset.

Adult↗

PubMed1996

Genetic architecture of common multifactorial diseases.

The purpose of this paper is to foster a dialogue among those interested in the genetic analysis of common chronic diseases. The need for an alternative to the Cartesian-Mendelian research strategy is discussed. A biological model that considers an individual's health to be an emergent property of a complex adaptive system is presented. A review of the contribution of the gene coding for apolipoprotein E to the genetic architecture of measures of lipid metabolism documents that an individual's coronary artery health has all the features expected of a complex adaptive system. Suggestions for enhancing our ability to use genetic information to predict onset, progression and severity of disease are offered.

Apolipoproteins E↗

PubMed1996

Genotypes with the apolipoprotein epsilon4 allele are predictors of coronary heart disease mortality in a longitudinal study of elderly Finnish men.

Earlier we reported that allelic variation in the gene coding for apolipoprotein (apoE is a significant predictor of variation in the risk of coronary heart disease (CHD) death in a longitudinal study of elderly Finnish men. Here we address the question: which of the apoE genotypes confers the risk information in these men, and whether such information persists after other CHD risk factors are considered? We followed two cohorts of elderly Finnish men aged 65 to 84 years, one in Eastern (n = 281) and the other in the Southwestern (n = 344) Finland for 5 years during which 26 (9.3%) of the men from the Eastern cohort and 40 (11.6%) of the men in the Southwestern cohort died from CHD. Baseline high density lipoprotein (HDL) cholesterol and (HDL cholesterol)2 in the Eastern cohort and age, and total and HDL cholesterol and smoking status in the Southwestern cohort were significant predictors of CHD death (P < 0.05). The apoE genotypes were significant predictors in the Southwestern cohort at P = 0.02 and in the Eastern cohort at P = 0.18. In multivariable models, information about apoE genotypes improved the prediction at P = 0.1O level of statistical significance in both cohorts. When genotypes were considered separately, the episilon2/4 combined with the epsilon4/4 in the Eastern cohort (odds ratio = 7.69, 95% CI = 1.67-35.52) and the epsilon 3/4 in the Southwestern cohort (odds ratio = 2.44, 95% CI = 1.165.10) had sigificantly greater odds of CHD death compared to the common F3/3 genotype. We conclude that apoE genotypes confer risk information about CHD death in two cohorts of elderly Finnish men in a longitudinal study, and this information persists after adjustment for other CHD risk factors. Because different genotypes were predictors in these two cohorts, we further conclude that the utility of a particular genotype as a predictor of CHD death in other populations may depend on the distribution of risk factor profiles at baseline, geographically defined environmental exposures, the CHD mortality history, and the evolutionary history of background genotypes in the population considered.

Age Factors↗

PubMed1996

Probability of having hypertension: effects of sex, history of hypertension in parents, and other risk factors.

The objective of the present study was to determine whether paternal and maternal history of hypertension contributes to the probability of an individual having hypertension before and after other measured traits, including sex, are considered. A cross-sectional sample of 217 men and 196 women was selected from the general Caucasion population of Rochester, Minnesota without respect to the hypertension status of subjects and their parents. Logistic regression analyses indicated that when no other information was considered, paternal history of hypertension contributed to the probability of having hypertension in men (chi 2 = 4.14, df = 1, p = 0.042) and in women (chi 2 = 4.12, df = 1, p = 0.042). The odds ratio associated with paternal history of hypertension was 2.80 in men (95% confidence interval [CI] = 1.0-8.0); the odds ratio was 4.11 in women (95% CI = 0.9-19.3). Maternal history of hypertension provided a marginally significant contribution to the prediction of probability of having hypertension in men (chi 2 = 3.86, df = 1, p = 0.049 in men), and less so in women (chi 2 = 3.31, df = 1, p = 0.068). The odds ratios associated with maternal history of hypertension were 2.85 in men (95% CI = 0.9-8.8) and 3.60 in women (95% CI = 0.8-16.9). A stepwise selection algorithm was used to select other predictors of hypertension in men and women. Other predictors of hypertension identified in men were age and sodium-lithium countertransport level. After these other predictors were considered, paternal but not maternal history of hypertension contributed to the probability of having hypertension in men. In a model that contained these other predictors, the partial odds ratio associated with paternal history of hypertension was 3.38 (95% CI = 1.1 = 10.1). Other predictors identified in women were age, apolipoprotein (apo) B, and apo B squared. After these other predictors were considered, neither paternal nor maternal history of hypertension made a statistically significant contribution to the probability of having hypertension in women. These results suggest that evaluation of the hypertension risk of an individual depends on the sex of the individual, the sexes of the individual's hypertensive parents, and the values of other measured risk factor traits.

Algorithms↗

PubMed1996

Genotype-environment interaction: apolipoprotein E (ApoE) gene effects and age as an index of time and spatial context in the human.

We analyzed the age-dependence of the estimates of the parameters of the genetic architecture of plasma ApoE levels associated with ApoE gene variation. Our study sample included 1988 individuals in multigeneration pedigrees from the Rochester, MN, population. We used a 30-yr sliding window across the age range (5-90 yr) to estimate the age dependency of parameters. Additive ApoE allelic variance of transformed plasma ApoE values for both genders, heritabilities for males and phenotypic and residual variance for females peaked in the 20-40-yr age windows and decreased significantly with age (P < 0.05). Phenotypic and residual variance for males and dominance variance for both genders did not vary significantly with age. All parameter estimates were significantly different from zero across all age windows for both genders. Most studies of ApoE have focused on its functions in the pathophysiology of coronary artery disease (CAD) in middle-aged and older individuals. Our findings suggest the greatest role of this gene is in determining phenotype differences among younger and middle-aged individuals. These observed genotypic effects on the plasma ApoE levels may contribute to age-dependent differences in physiological health, growth, and risk of disease.

Adolescent↗

PubMed1996

Association of genetic variation with interindividual variation in ambulatory blood pressure.

OBJECTIVE: To determine whether genetic and non-genetic components of interindividual variation in systolic and diastolic blood pressure are constant throughout the day or are time or activity dependent. METHODS: We obtained 24 h ambulatory blood pressure recordings in 263 members of 68 unrelated nuclear families (i.e. parents and their offspring) representative of the Caucasian population of Rochester, MN, USA. Using the time each patient got into bed as a reference point, we identified 198 records in which this reference point was preceded by eight consecutive active hours (out of bed) and followed by four consecutive inactive hours (in bed) in which four or more blood pressure readings taken each hour were judged to be technically satisfactory. For each hourly mean for systolic and diastolic blood pressure, we estimated total interindividual variance, variance associated with concomitant variables (generation; sex within generation strata; and age, height, weight, body mass index, and abdomen-to-hip ratio within generation and sex strata), and variance associated with additive genetic effects (i.e. the chief cause of resemblance between relatives). To assess trends in each component of interindividual blood pressure variance over the 12 h period, we estimated the slope of the linear regression line fit to the hourly estimates. RESULTS: For systolic blood pressure, total interindividual variance did not change significantly (slope of regression line = -0.23, P = 0.717). In contrast, total interindividual variance for diastolic blood pressure was greater during active hours than inactive hours (slope of regression line = -5.53, P < 0.001). For both systolic and diastolic blood pressure, variance associated with the concomitant variables was greater during active hours than during inactive hours (for systolic blood pressure slope of regression line = -2.98, P = 0.001; for diastolic blood pressure slope of regression line = -6.14, P < 0.001). Likewise, for both systolic and diastolic blood pressure, variance associated with additive genetic effects was also greater during active hours than during inactive hours (for systolic blood pressure slope of regression line = -1.65, P = 0.090; for diastolic blood pressure slope of regression line = -1.47, P = 0.018). CONCLUSIONS: This study demonstrates that components of interindividual variation in blood pressure are not constant, but are time or activity dependent.

Adolescent↗