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Biomedical subjects

S C Hunt

Publications and source records attributed to S C Hunt.

At least 37 records · Page 2Linked to original sources
PubMed2000

Segregation analysis of serum uric acid in the NHLBI Family Heart Study.

Segregation analysis was performed on the serum uric acid measurements from 523 randomly ascertained Caucasian families from the NHLBI Family Heart Study. Gender-specific standardized residuals were used as the phenotypic variable in both familial correlation and segregation analysis. Uric acid residuals were adjusted for age, age2, age3, body mass index (kg/m2), creatinine level, aspirin use (yes/no), total drinks (per week), HOMA insulin resistance index [(glucose * insulin)/22.5], diuretic use (yes/no), and triglyceride level. Sibling correlations (r=0.193) and parent-offspring correlations (r=0.217) were significantly different from zero, but these two familial correlations were not significantly different from one another. After adjustment for covariates, the heritability estimate for serum uric acid was 0.399. Segregation analysis rejected the "no major gene" model but was unable to discriminate between an "environmental" and a "Mendelian major gene" model. These results support the hypothesis that uric acid is a multifactorial trait possibly influenced by more than one major gene, modifying genes, and environmental factors.

Arteriosclerosis↗
PubMed2000

Functional status and emotional well-being, dietary intake, and physical activity of severely obese subjects.

OBJECTIVE: Analyze functional status and emotional well-being, energy and nutrient intake, and physical activity in sibling pairs raised together in the same family. DESIGN: One sibling classified as severely obese (body mass index > or = 35) and the other sibling as normal weight (body mass index < or = 27). SUBJECTS: From January 1994 through December 1996 at the Cardiovascular Genetics Research Clinic of the University of Utah School of Medicine, 145 sibling pairs (n = 290) were selected from a population-based, family history database or a hospital-based, very-low-energy weight-loss program. STATISTICAL ANALYSIS PERFORMED: Repeated-measures analysis of variance tested for differences between severely obese and normal-weight siblings. RESULTS: All functional status and emotional well-being scores (poorer perceived health) were significantly lower in severely obese siblings compared with normal-weight siblings. The severely obese siblings had a higher percentage dietary fat intake (3% higher) and total energy intake (more than 350 kcal higher), and lower weight-adjusted total energy intake (almost 10 kcal/kg lower) and activity energy expenditure (3.5 kcal/kg lower), compared with normal-weight siblings. Thus, environmental influences such as energy and nutrient intake and physical activity are highly related to severe obesity. APPLICATIONS: Previously shared environment of severely obese and normal-weight siblings raises questions about whether strong environmental influences or genetic predisposition account for the differences in sibling weight. When counseling individuals or families with a history of severe obesity, dietetics practitioners should be familiar with the potential for strong genetic factors and related environmental influences. In addition, dietitians should be prepared to offer a flexible approach to physical exercise as well as provide additional behavioral support.

Adult↗
PubMed2000

Influence of leisure time physical activity and television watching on atherosclerosis risk factors in the NHLBI Family Heart Study.

Physical activity favorably influences atherosclerosis risk factors but only a few studies in adults considered the time watching television (TV) as a measure of physical inactivity. We therefore determined in a population-based sample of 1778 subjects from the NHLBI Family Heart Study (FHS) whether leisure time physical activity and TV watching have independent or interactive associations with cardiovascular disease risk factors and carotid artery intima-media wall thickness (IMT). Subjects were free from diabetes mellitus and clinically-ascertained coronary artery disease and did not take lipid-lowering or antihypertensive drugs. Only 0.7 and 1.3% of the variance in leisure time physical activity in women and men, respectively, was explained by the amount of TV watching. Leisure time physical activity had a clearly favorable, and TV watching an unfavorable association with anthropometric measurements (BMI (body mass index), waist girth, waist-hip ratio, subscapular and triceps skinfold thickness). The odds ratio (95% CI) of being overweight was 0.41 (0.28-0.62) in women and 0.69 (0.46-1.04) in men in the highest quartile of leisure time physical activity compared to the lowest quartile. The odds ratio increased for increasing quartiles of TV watching to 2.12 (1.45-3.10) in women and 1.61 (1.07-2.43) in men. Watching TV only 1 h per day in women with a BMI of 30 kg/m2 and doing about 75 min of moderate exercise per week was associated with a BMI 1.8 kg/m2 lower than in women watching TV 3 h per day and doing the same amount of exercise. Those with twice the amount of moderate exercise and watching TV 1 h per day had a BMI 0.45 kg/m2 lower. Furthermore, leisure time physical activity was negatively associated with concentrations of triglycerides and positively with HDL cholesterol in both genders. TV watching was significantly positively associated with triglycerides and slightly negatively with HDL cholesterol in men. The observed associations of leisure time physical activity and TV watching with atherosclerosis risk factors were independent from each other. Finally, we analyzed the relation between leisure time physical activity, TV watching and the degree of IMT of the carotid arteries. Neither of these two measures was significantly associated with IMT. In summary, TV watching, in addition to leisure time physical activity, shows an independent association with obesity-related anthropometric measurements, HDL and triglycerides. Decreasing the amount of TV watching might be effective as a first step in reducing atherosclerosis risk factors, especially overweight.

Adult↗
PubMed2000

No evidence of linkage between the very-low-density lipoprotein receptor gene and fasting serum insulin or homeostasis model assessment insulin resistance index: the National Heart, Lung, and Blood Institute Family Heart Study.

A major gene effect on the fasting insulin level and insulin resistance has been suggested in previous studies. Several candidate genes for insulin resistance in rare syndromes have been proposed. However, there has been limited success in finding genes for common forms of insulin resistance. There is accumulating evidence of a relationship between insulin resistance and a disturbance of free fatty acid (FFA) metabolism. The very-low-density lipoprotein (VLDL) receptor, which is associated with FFA metabolism, could serve as a possible candidate gene for insulin resistance. We performed linkage analyses between the VLDL receptor gene and fasting insulin and the homeostasis model assessment (HOMA) insulin resistance index (fasting insulin x fasting glucose/22.5) in 1,050 sibpairs participating in the phase II physical examination of the National Heart, Lung, and Blood Institute Family Heart Study (FHS). Data analyses were completed using the SIBPAL component of the SAGE software package (SAGE, Statistical Analysis for Genetic Epidemiology, Version 3.1; Computer program package available from the Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, 1997). We did not find evidence for linkage of the fasting insulin or the HOMA insulin resistance index with a polymorphic marker at the VLDL locus (P = .316 and .402, respectively). Adjustment of fasting insulin and the HOMA insulin resistance index for the body mass index (BMI) did not change the results (P = .319 and .472, respectively). In conclusion, no evidence was found for a linkage between a locus controlling the fasting insulin level or HOMA insulin resistance index and a VLDL polymorphism in the present study. Additional adjustment of fasting insulin or the HOMA insulin resistance index for the BMI did not change the linkage results significantly.

Blood Glucose↗
PubMed2000

Insulin and hypertension in the NHLBI Family Heart Study: a sibpair approach to a controversial issue.

The association between insulin and hypertension remains equivocal. We therefore investigated insulin levels in 3037 normotensive and 1067 hypertensive subjects from the National Heart, Lung and Blood Institute (NHLBI) Family Heart Study (FHS) by two different approaches. First, we compared insulin levels between normotensive and 275 untreated hypertensive subjects. Insulin levels unadjusted as well as adjusted for age, sex, and center were significantly higher in hypertensives. After adjustment for body mass index (BMI), insulin remained significantly higher only in the diastolic hypertensive group (mean +/- SD 77.0 +/-36.7 pmol/L, P < .01) but not in the isolated systolic hypertensive group (67.0 +/- 38.2 pmol/L) when compared to normotensives (63.2 +/- 29.1 pmol/L). A sibpair analysis was then used that compared the intra-sibpair differences in insulin concentrations to the intra-sibpair differences in blood pressure (BP) levels. This approach was intended to control for the effects of genetic and residual shared environmental variance upon insulin levels. The intra-sibpair difference in insulin concentrations between concordant (diastolic and systolic deltaBP < 5 mm Hg) and discordant sibpairs (diastolic and systolic deltaBP > 15 and > 20 mm Hg, respectively) was no longer significantly different when adjusted for BMI (2.7 v 5.9 pmol/L for diastolic and -1.7 v -1.8 pmol/L for systolic BP). Even the random selection of one sibpair from each of the 326 families independently of insulin and BP levels did not result in a significant correlation between the intrasibpair differences in insulin and BP. Using an insulin resistance index instead of insulin did not change our findings. Our investigation in the FHS sample of families suggests that there is only a small, if any, influence of insulin levels on BP after adjustment for obesity-related sources of variation.

Adult↗
PubMed2000

Association between the alpha-adducin gene and hypertension in the HyperGEN Study.

This report from the HyperGEN Study, one of four networks participating in the NHLBI-sponsored Family Blood Pressure Program, presents the results of an association study based on 822 white and 572 black subjects (cases and controls) participating in the HyperGEN Network from five geographically diverse field centers. All cases met the Joint National Committee on Detection and Treatment of High Blood Pressure (JNC VI) criteria for hypertension (Stage I or higher). Each subject was clinically examined for risk factors for hypertension as well as genotyped for the point mutation Gly460Trp at the alpha-adducin locus on chromosome 4p. In the white group, the prevalence of genotypes with one or more Trp alleles was 26% in normotensives, versus 33% in hypertensives randomly selected from the population, and 39% among the multiply affected hypertensive sibships. Overall, in whites, the Trp allele significantly increased the odds of hypertension (P = .0056), with an odds ratio (OR) of 1.73 (95% confidence interval [CI] = 1.17, 2.54). The alpha-adducin gene remained a significant independent predictor of hypertension in a multivariate logistic model even after correcting for other risk factors for hypertension, including gender, age, body mass index (BMI), smoking, LDL cholesterol, triglycerides, urine sodium (Na), and urine potassium (K), (OR = 1.55, 95% CI = 1.03, 2.34). Through the use of regression trees, several gene-by-environment interactions were implicated, suggesting that alpha-adducin appears to be a particularly important risk factor (OR = 4.2) for older (age > 60.5 years), less lean (BMI < 25.8 kg/m2) subjects with moderately high triglycerides (between 145.5 and 218.5 mg/dL). In the black group, the relationship was less clear. Overall, it was protective against hypertension. The prevalence of genotypes with one or more Trp alleles was 24% among normotensive versus 11% in hypertensive black subjects randomly selected from the population, and 13% among multiply affected hypertensive sibships, resulting in an OR of 0.48 (P = .0231; 95% CI = 0.25, 0.90). However, the Trp genotype was no longer a significant independent predictor of hypertension risk in the multivariate logistic model (OR = 0.79; 95% CI = 0.37, 1.67), suggesting that it may be operating through one or more of these other factors. Thus, we conclude that the alpha-adducin gene is a significant, independent risk factor for hypertension in whites, but not in blacks, and may play a particularly important role for subjects with certain constellations of other risk factors.

Alleles↗
PubMed2000

NHLBI family blood pressure program: methodology and recruitment in the HyperGEN network. Hypertension genetic epidemiology network.

PURPOSE: Hypertension is a common precursor of serious disorders including stroke, myocardial infarction, congestive heart failure, and renal failure in whites and to a greater extent in African Americans. Large genetic-epidemiological studies of hypertension are needed to gain information that will improve future methods for diagnosis, treatment, and prevention of hypertension, a major contributor to cardiovascular morbidity and mortality. METHODS: We report successful implementation of a new structure of research collaboration involving four NHLBI "Networks," coordinated under the Family Blood Pressure Program. The Hypertension Genetic Epidemiology Network (HyperGEN) involves scientists from six universities and the NHLBI who seek to identify and characterize genes promoting hypertension. Blood samples and clinical data were projected to be collected from a sample of 2244 hypertensive siblings diagnosed before age 60 from 960 sibships (half African-American) with two or more affected persons. Nonparametric sibship linkage analysis of over one million genotype determinations (20 candidate loci and 387 anonymous marker loci) was projected to have sufficient power for detecting genetic loci promoting hypertension. For loci showing evidence for linkage in this study and for loci reported linked or associated with hypertension by other groups, genotypes are compared in hypertensive cases versus population-based controls to identify or confirm genetic variants associated with hypertension. For some of these genetic variants associated with hypertension, detailed physiological and biochemical characterization of untreated adult offspring carriers versus non-carriers may help elucidate the pathophysiological mechanisms that promote hypertension. RESULTS: The projected sample size of 2244 hypertensive participants was surpassed, as 2407 hypertensive individuals (1262 African-Americans and 1145 whites) from 917 sibships were examined. Detailed consent forms were designed to offer participants several options for DNA testing; 94% of participants gave permission for DNA testing now or in the future for any confidential medical research, with only 6% requesting restrictions for tests performed on their DNA. Since this is a family study, participants also are asked to list all first degree relatives (along with names, addresses, and phone numbers) and to indicate for each relative whether they were willing to allow study staff to make a contact. Seventy percent gave permission to contact some relatives; about 30% gave permission to contact all first degree relatives; and less than 1% asked that no relatives be contacted. Successes after the first four years of this study include: 1) productive collaboration of eight centers from six different locations; 2) early achievement of recruitment goals for study participants including African-Americans; 3) an encouraging rate of consent for DNA testing (including future testing) and relative contacting; 4) completed analyses of genetic linkage and association for several candidate gene markers and polymorphisms; 5) completed genotyping of random markers for over half of the full sample; and 6) early sharing of results among the four Family Blood Pressure Program networks for candidate and genome search analyses. CONCLUSIONS: Experience after four years of this five-year program (1995-2000) suggests that the newly initiated NHLBI Network Program mechanism is fulfilling many of the expectations for which it was designed. It may serve as a paradigm for future genetic research that can benefit from large sample sizes, frequent sharing of ideas among laboratories, and prompt independent confirmation of early findings, which are required in the search for common genes with relatively small effects such as those that predispose to human hypertension.

Adult↗
PubMed2000

Inheritance of the waist-to-hip ratio in the National Heart, Lung, and Blood Institute Family Heart Study.

OBJECTIVE: Considering that waist-to-hip ratio (WHR) is a simple anthropometric measure of obesity and is a better predictor of coronary heart disease than body mass index (BMI), the genetic underpinnings of WHR are of interest. The inheritance pattern of WHR, before and after adjustment for BMI (WHR-BMI), was investigated in 2713 individuals from 1038 nuclear families in the National Heart, Lung, and Blood Institute Family Heart Study (NHLBI-FHS). RESEARCH METHODS AND PROCEDURES: Waist and hip measurements were taken twice, and the means of the measurements were used to calculate the WHR. Adjustments for age were carried out separately by sex, using stepwise multiple regression procedures for WHR and WHR-BMI phenotypes. Segregation analysis was applied using the unified model as implemented in the computer program POINTER. RESULTS: For age-adjusted WHR, the segregation results suggested an additive major gene that accounts for 35% of the phenotypic variance, and approximately 30% of the sample are homozygous for the "high" genotype. The results for age- and BMI-adjusted WHR were also compatible with a major gene; however, the multifactorial model provided the most parsimonious fit to the data. DISCUSSION: Although the genetic mechanisms for several obesity traits have been studied, tests of Mendelian segregation on this simple anthropometric measure (WHR) have not been reported previously. This study provides evidence for the presence of a major gene for age-adjusted WHR, suggesting that it is an appropriate trait for further genetic analysis, especially because it has strong predictive value and probably relates biologically to cardiovascular risk.

Body Constitution↗
PubMed2000

Linkage of human tumor necrosis factor-alpha to human osteoporosis by sib pair analysis.

Osteoporosis as well as osteopenia are common human conditions considered to result from the interplay of multiple genetic and environmental factors. Twin and family studies have yielded strong correlation between measures of bone mass and a number of genetic factors. Certain genes (e.g., cytokines such as interleukin-1, interleukin-6, or tumor necrosis factor-alpha) are capable of regulating metabolism, formation, and resorption of bone; all processes that determine bone mass. We tested 192 sib-pairs of adult Japanese women from 136 families for genetic linkage between osteoporosis and osteopenia phenotypes and allelic variants at the tumor necrosis factor-alpha (TNFA) locus, using a dinucleotide-repeat polymorphism located near the gene. The TNFA locus showed evidence for linkage to osteoporosis, with mean allele sharing of 0.478 (P = 0.30) in discordant pairs and 0.637 (P = 0.001) in concordant affected pairs. Linkage with osteopenia was also significant in concordant affected pairs (P = 0.017). Analyses limited to the post-menopausal women in our cohort showed similar or even stronger linkage for both phenotypes. The results provide evidence that genetic variations within the TNFA locus or adjacent genes affect regulation of mineral metabolism in bone and some of them confer risk for osteoporosis in adult women.

Adult↗
PubMed2000

Effects of gender and genotype on the phenotypic expression of nonmodulating essential hypertension.

Nonmodulation describes a subset of the normal/high renin essential hypertensive population. It is an inherited trait. This report reviews the genetic and gender data recently available that discuss the modification of the expression of the nonmodulating phenotype. Both the adrenal and the renal blood flow markers for nonmodulation are associated with a single nucleotide polymorphism (SNP) in the coding region of the angiotensinogen gene at codon 235. Even though the nonmodulating phenotype is associated with a somatic gene, gender modifies its expression. In women, the expression of the nonmodulating phenotype is approximately half of that in men. Additional analysis suggests that this gender difference is almost entirely explained by a difference in the frequency of nonmodulation in younger premenopausal women. In older, likely postmenopausal women, there is no gender difference. This suggests that the expression of the nonmodulating phenotype, presumably secondary to changes in the expression of the angiotensinogen gene, is modulated by female sex hormones.

Female↗
PubMed2000

Lack of association between the angiotensin-converting enzyme insertion/deletion polymorphism and plasminogen activator inhibitor-1 antigen levels in the National Heart, Lung, and Blood Institute Family Heart Study.

Experimental and clinical research supports a direct link between activation of the renin-angiotensin system and production of plasminogen activator inhibitor-1 (PAI-1), the primary physiologic inhibitor of tissue plasminogen activator. Several studies have reported higher PAI-1 levels in individuals carrying the deletion (D) allele of the angiotensin-converting enzyme (ACE) gene. We investigated the association between ACE genotypes and plasma PAI-1 levels in a family study of 577 women and 428 men from four US communities. Participants were between 25 and 84 years of age without evidence of coronary heart disease (CHD). Mean geometric plasma PAI-1 levels adjusted for ethnicity were 17.4, 17.9, and 18.1 ng/ml in participants with the DD, insertion-deletion (ID), and II genotypes, respectively (P = 0.89 for difference). We found no associations between ACE I/D genotypes and plasma PAI-1 antigen concentrations in a subset of participants without major CHD risk factors (hypertension, hypercholesterolemia, overweight, smoking, diabetes) or in a small sample of African-Americans. Our findings suggest that the ACE insertion/deletion polymorphism has relatively little, if any, influence on circulating PAI-1 levels in the population at large.

Adult↗
PubMed2000

Evaluation of heterodimeric guanylyl cyclase genes as candidates for human hypertension.

OBJECTIVE: Both physiologic and pharmacological data have implicated the nitric oxide (NO) signaling cascade in the regulation of blood pressure in humans and its impairment in the pathogenesis of hypertension. In biological systems, the principal receptor for NO is NO-stimulated guanylyl cyclase. NO-stimulated guanylyl cyclases are obligate heterodimers (alpha/beta). The genes for guanylyl cyclase subunits alpha1, beta, and beta2 are likely candidates for causing hypertension in the Dahl rat as their expression is altered and their gene loci are closely linked to known quantitative trait loci for blood pressure in Dahl rat crosses. The objective of the current study was to test whether markers near guanylyl cyclase subunit genes were linked to hypertension in Caucasians. DESIGN: To test for linkage of genetic markers in or near the guanylyl cyclase genes to hypertension in Caucasians, a sample of 124 Utah hypertensive sib pairs was genotyped. RESULTS: Four highly polymorphic markers in or near the human guanylyl cyclase subunits homologous to the rat alpha1 (human chromosome 8), rat beta1 (human chromosome 4), and rat beta2 (human chromosome 13) genes showed no evidence of excess allele sharing in the set of hypertensive sibships. CONCLUSION: We conclude that the heterodimeric guanylyl cyclase subunit loci do not appear to be linked to hypertension in Caucasians.

Adult↗
PubMed2000

Replication of linkage of familial combined hyperlipidemia to chromosome 1q with additional heterogeneous effect of apolipoprotein A-I/C-III/A-IV locus. The NHLBI Family Heart Study.

Familial combined hyperlipidemia (FCHL), the most common familial dyslipidemia, is implicated in up to 20% of cases of premature coronary heart disease. Although underlying mutations for FCHL have yet to be identified, several candidate genes/regions have been identified. A positive linkage to chromosome 1q markers has been reported, with the highest lod score of 5.93 occurring at a location between D1S104 and D1S1677. Using the same diagnostic criteria, the Family Heart Study (FHS) has defined 71 FCHL families, comprising 170 cases, for a total of 137 possible affected sibling pairs. The FCHL criteria require elevation in serum low density lipoprotein cholesterol and triglyceride levels within the family, with at least 2 affected first-degree relatives. Markers D1S104 and D1S1677 were typed, and significant allele sharing was found in FCHL sibships (multipoint lod score with use of the model from the Finnish study was 2.52, and multipoint nonparametric score was 2.48; P=0.007), replicating linkage in this chromosome 1 region. In addition, previously reported linkage of FCHL to apolipoprotein A-I/C-III/A-IV has been investigated in FHS families. FHS results revealed positive but nonsignificant allele sharing among FCHL sibships with apolipoprotein A-I/C-III/A-IV by use of marker D11S4127 (nonparametric linkage score 1.11, P=0.13). Two-locus analyses of D1S104 and D11S4127 suggested possible heterogeneity rather than epistasis, with a maximum 2-locus lod score of 3.05. A nonparametric 2-locus analysis revealed significant improvement in the 2-locus versus single-locus scores. Finally, no linkage was found with markers near the lipoprotein lipase gene region.

Alleles↗
PubMed2000

Genetic localization to chromosome 1p32 of the third locus for familial hypercholesterolemia in a Utah kindred.

Clinical familial hypercholesterolemia has been shown to result from mutations in 2 genes, the low density lipoprotein (LDL) receptor on chromosome 19 and apolipoprotein B on chromosome 2. However, we have recently described a Utah pedigree in which linkage to both genes was clearly excluded. A multipoint linkage analysis of 583 markers genotyped on 31 (18 affected) members of this pedigree was undertaken to localize a genetic region that may harbor a third gene that could result in clinical familial hypercholesterolemia. A multipoint log of the odds score of 6.8 was obtained for markers on 1p32. Haplotype carriers and affected status are completely concordant (18/18 persons). The phenotype is also expressed in young children (ages 4 and 9). Specific recombinant individuals in the pedigree restrict the region of linkage to an approximately 17 cM interval between polymorphic markers D1S2130 and D1S1596. This region appears to overlap the region found linked to severe hypercholesterolemia in French and Spanish families. The identification of the gene in this region may provide important pathophysiological insights into new mechanisms that may lead to highly elevated LDL cholesterol and other associated dyslipidemic phenotypes.

Adolescent↗
PubMed2000

Aldosterone stimulation by angiotensin II : influence of gender, plasma renin, and familial resemblance.

The aldosterone response to infused angiotensin II (Ang II) in patients receiving a low-salt diet has been described as an important phenotype for genetic studies on human hypertension. The objectives of the present study were to determine the parameters that influence this intermediate phenotype as a quantitative trait and to assess the importance of its familial resemblance in hypertensive sibling pairs. Two hundred one white hypertensive subjects (95 families: 84 pairs and 11 trios) were selected in 3 centers. The patients followed the same protocol, which included a 4-week withdrawal period of antihypertensive therapy, a 1-week period on a low-salt diet, and a 30-minute infusion of Ang II. The increase in the aldosterone level was greater in women than in men (29.1+/-16.2 versus 18.2+/-9.6 ng/dL, P<0.0001). A strong relationship was found with age (r=-0.54, P<10(-4)) and plasma renin activity (r=0.32, P<10(-4)) in women but not in men. Weak correlations of the aldosterone response to Ang II were observed for the whole set of sibling pairs (r=0.11, NS). Conversely, strong sibling correlations were found among brother-brother pairs (r=0.40, n=36) and among sister-sister pairs as soon as age or menopausal status was considered. Similar results were obtained when the Ang I-aldosterone response was analyzed as a qualitative trait (kappa=0. 35, P<0.008 in brother-brother pairs). We conclude that age, gender, and plasma renin are strong determinants of the aldosterone response to Ang II, with strong sibling correlations in men and postmenopausal women. These relationships will have to be considered in future linkage and association studies.

Adult↗
PubMed2000

Possible locus on chromosome 18q influencing postural systolic blood pressure changes.

We conducted a genome-wide scan for quantitative trait loci influencing the systolic blood pressure, diastolic blood pressure, and pulse responses to a postural challenge in 498 white sibling-pairs from the Hypertension Genetic Epidemiology Network, a multicenter study of the genetic susceptibility to hypertension. All participants were hypertensive (systolic blood pressure >/=140 mm Hg, diastolic blood pressure >/=90 mm Hg, or on antihypertensive medications) with diagnosis before age 60. Blood pressure and pulse were measured by an oscillometric method after a 5-minute rest in a supine position and again immediately on standing. The genome scan included a total of 387 autosomal short-tandem-repeat polymorphisms typed by the National Heart, Lung, and Blood Institute Mammalian Genotyping Service at Marshfield. We used multipoint variance-components linkage analysis to identify possible quantitative trait loci influencing postural change phenotypes after adjusting for sex, age, and use of antihypertensive medications. There was suggestive evidence for linkage on chromosome 18q for the postural systolic blood pressure response (maximum logarithm of the odds score=2.6 at 80 centiMorgans). We also observed a maximum logarithm of the odds score of 1.9 for the systolic blood pressure response and 1.7 for the diastolic blood pressure response on chromosome 6p. The marker that demonstrated the strongest evidence for linkage for the systolic blood pressure response (D18S858) lies within 20 centiMorgans of a marker previously linked to rare familial orthostatic hypotensive syndrome. Our findings indicate that there may be 1 or more genes on chromosome 18q that regulate systolic blood pressure during the physiological recovery period after a postural stressor.

Age Distribution↗