Biomedical subjects

N Schork

Publications and source records attributed to N Schork.

At least 19 recordsLinked to original sources

PubMed1999

Blood pressure and the T174M and M235T polymorphisms of the angiotensinogen gene.

PURPOSE: The angiotensinogen gene (AGT), which encodes the precursor of the vasoactive hormone angiotensin II, has been reported to be associated with hypertension in Caucasian and Japanese populations. We examined the relationship between two common molecular variants of AGT, T174M and M235T and blood pressure in two cohorts from the Anqing region of China. Cohort I (N = 794) consisted of families ascertained by either hypertensive or hypotensive siblings; and Cohort II (N = 761) represented a collection of randomly selected families. METHODS: Blood pressure was measured according to standard protocols, and information on age, sex, body mass index, alcohol consumption, and cigarette smoking was collected by trained interviewers using standardized questionnaires. The association of AGT genotypes and blood pressure was examined in multivariate linear regression models, with adjustment for potential intrafamilial correlations. The respective T and M allele frequencies for T174M were 0.93 and 0.07, and 0.80 and 0.20 for M235T among the parents for randomly selected families. All the analyses were conducted after exclusion of individuals currently under antihypertensive medication. RESULTS: In the pooled analysis of the two cohorts, neither the T174M nor the M235T polymorphism was significantly associated with variations of blood pressure assuming a recessive (T174M: p = 0.73 and 0.61; M235T: p = 0.99 and 0.24; for SBP and DBP), dominant (T174M: p = 0.54 and 0.72; M235T: p = 0.79 and 0.12; for SBP and DBP), or additive (T174M: p = 0.52 and 0.67, M235T: p = 0.91 and 0.11; for SBP and DBP) model. Likewise, no statistically significant association was detected when the two cohorts were analyzed separately. The logistic regression analysis of hypertension also failed to reveal any association with these markers. CONCLUSIONS: In summary, our analyses suggest that the molecular variants of AGT may not be associated with variations of blood pressure in this rural Chinese population.

Adolescent↗

PubMed1999

Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment.

Clinically similar asthma patients may develop airway obstruction by different mechanisms. Asthma treatments that specifically interfere with the 5-lipoxygenase (ALOX5) pathway provide a method to identify those patients in whom the products of the ALOX5 pathway (that is, the leukotrienes) contribute to the expression of the asthma phenotype. Failure of an asthma patient to respond to treatment with ALOX5-pathway modifiers indicates that leukotrienes are not critical to the expression of the asthmatic phenotype in that patient. We previously defined a family of DNA sequence variants in the core promoter of the gene ALOX5 (on chromosome 10q11.2) associated with diminished promoter-reporter activity in tissue culture. Because expression of ALOX5 is in part transcriptionally regulated, we reasoned that patients with these sequence variants may have diminished gene transcription, and therefore decreased ALOX5 product production and a diminished clinical response to treatment with a drug targeting this pathway. Such an effect indicates an interaction between gene promoter sequence variants and drug-treatment responses, that is, a pharmacogenetic effect of a promoter sequence on treatment responses.

Alleles↗

PubMed1999

Mapping of a blood pressure quantitative trait locus to chromosome 15q in a Chinese population.

Blood pressure is a complex trait of pivotal biological importance, in which 20-50% of interindividual variation is genetically determined. Whereas genes have been identified in several rare Mendelian forms of hypertension, little progress has been made in understanding the genetics of blood pressure variation in the general population. Recently, we screened the human genome using rural Chinese sibling pairs with extreme blood pressure and identified suggestive linkage for two chromosomal regions. By refining the trait definition and genotyping additional markers, we detected significant linkage (maximum lod score = 3.77) near D15S203 in lower extreme diastolic blood pressure sibling pairs. Using a second independent data set from the same geographical area, we marginally replicated ( P = 0.05) this result, suggesting that this locus is very likely to be involved in the regulation of diastolic blood pressure.

Adult↗

PubMed1997

Comparison of phenotype between patients with Prader-Willi syndrome due to deletion 15q and uniparental disomy 15.

Prader-Willi syndrome (PWS) is a complex multiple anomaly syndrome that has been shown to result from deficient expression of paternal chromosome 15(q11-q13). In most cases, it is caused either by deletion of this region in the paternally inherited chromosome 15 or by maternal uniparental disomy (UPD) of chromosome 15. In order to determine whether there are phenotypic differences between patients whose PWS is caused by these two different mechanisms, 54 affected individuals (37 with deletion, 17 with UPD) were personally examined and studied using molecular techniques. The previously recognized increased maternal age in patients with UPD and increased frequency of hypopigmentation in those with deletion were confirmed. Although the frequency and severity of most other manifestations of PWS did not differ significantly between the two groups, those with UPD were less likely to have a "typical" facial appearance. In addition, this group was less likely to show some of the minor manifestations such as skin picking, skill with jigsaw puzzles, and high pain threshold. Females and those with UPD were also older, on average. Possible mechanisms by which these differences could occur and the implications of these differences for diagnosis are described.

Adolescent↗

PubMed1995

Blood pressure in genetically hypertensive rats. Influence of the Y chromosome.

We used a cross between the stroke-prone spontaneously hypertensive rat (SHRSP) strain and the Wistar-Kyoto (WKY) normotensive strain to elucidate the genetic basis of hypertension. Previous studies have reported conflicting evidence for the contribution of the Y chromosome to hypertension in these models. To investigate further the role of the Y chromosome in hypertension, we performed two large reciprocal crosses: one with the SHRSP as a male progenitor of the cross, yielding 60 F2 rats, and another with the WKY as a male progenitor, yielding 83 F2 rats. The resulting F2 hybrids were phenotyped with the use of a radiotelemetry system (Data Sciences) for measurement of systolic, diastolic, and mean arterial pressures as well as heart rate and motor activity continuously for 96 hours at baseline and after 1% NaCl was added to the rats' drinking water for 12 days. Male F2 hybrids with the SHRSP grandfather had significantly higher average systolic, diastolic, and mean arterial pressures at baseline compared with male F2 hybrids with the WKY grandfather (188.7 +/- 18.1 versus 168.9 +/- 11.5, 130.3 +/- 14 versus 115.7 +/- 7.3, and 159.1 +/- 15.8 versus 141.5 +/- 9.4 mm Hg, respectively). These differences were also observed after salt loading (197.9 +/- 22.1 versus 176.8 +/- 11.7, 136.5 +/- 17.3 versus 120.7 +/- 7.6, and 166.7 +/- 19.5 versus 148 +/- 9.7 mm Hg, respectively; P < .0001 for each comparison). These results suggest that the SHRSP Y chromosome contains a locus or loci that contribute to hypertension in SHRSP/WKY F2 hybrids.

Animals↗

PubMed1994

Recreational exercise and cardiovascular status in the rural community of Tecumseh, Michigan.

BACKGROUND: Because of population stability, Tecumseh, a rural community in Michigan, was the site of health surveys over a period of three decades. METHODS: In the recent survey anthropometrics, blood pressure (BP), blood chemistry, echo/Doppler cardiac exam, personality and exercise questionnaires were collected on site. RESULTS: In this rural community 70% of subjects (447 men, 410 women, average age 30 years) do not engage in recreational exercise. Sedentary subjects were heavier (4 kg), had higher BP (2.3/2 mm Hg), faster heart rate (4 beats/min), and lower stroke volume (2 ml/m2) than physically more active subjects (p = 0.02 to 0.00001). Measures of cardiac structure and function were more favorable in exercising subjects. Cholesterol (+8 mg/dl), triglycerides (+15 mg/dl) and insulin (+2.4 microU/ml) were higher and HDL cholesterol was lower (-2 mg/dl) in the sedentary group (p = 0.04 to 0.003). Being sedentary was associated with more anxiety, anger and feeling time pressure (p = 0.001 to 0.00001). Exercise demands at work had no effect while even once a week recreational exercise was associated with a more favorable cardiovascular risk status. A difference in cardiovascular status between the sedentary and exercising subjects was not apparent throughout childhood, adolescence or early adult life, suggesting that subjects who exercise presently were not a priori healthier than presently sedentary subjects. CONCLUSIONS: Seventy percent of the residents studied in Tecumseh are physically inactive and have a less favorable cardiac risk profile. Enhancement of exercise habits may beneficially affect cardiovascular status and, presumably, the prognosis.

Adolescent↗

PubMed1994

Hematocrit levels and physiologic factors in relationship to cardiovascular risk in Tecumseh, Michigan.

OBJECTIVE: To investigate the relationship between hematocrit, blood pressure and other known cardiovascular risk factors. DESIGN: The Tecumseh Blood Pressure Study includes a cohort of subjects of average age 29.5 years (346 male, 277 female) who reside in Tecumseh, Michigan, USA. METHODS: The body weight; home, work and clinic blood pressures; hematocrit level, plasma renin activity, baseline and mentally stimulated plasma catecholamines level; and fasting glucose, insulin and lipids levels were obtained. Since menstruation and childbearing affect the hematocrit, results are presented only for males. The males in Tecumseh were divided into tertiles of hematocrit (group I < or = 43.25, group II 43.26-45.2 and group III > 45.2%). RESULTS: Higher hematocrit levels were significantly related to higher blood pressures at home, at work and in the clinic, although all of the values measured were within the normotensive range (128/79 mmHg clinic blood pressure in group III). The metabolic factors weight, cholesterol, triglycerides, insulin and glucose levels were significantly elevated in group III. The weight affected only the relationship of hematocrit to plasma insulin levels and not the other variables including the blood pressure. Groups II and III showed signs of sympathetic overactivity; their plasma renin levels, heart rates and norepinephrine levels after mental stimulation were elevated. CONCLUSIONS: Although the relationship of blood pressure to the hematocrit level was previously known, in Tecumseh hematocrit is also found to be associated with several other cardiovascular risk factors and with signs of a hypersympathetic state. We intend to evaluate prospectively the relative prognostic significance of a higher hematocrit level versus the other associated risk factors.

Adult↗

PubMed1993

Effects of fluoxetine on the oral environment of bulimics.

The purpose of this study was to evaluate in a double-blind placebo-based study the effects of fluoxetine over a period of 16 weeks on the frequency of binging and purging and on fluctuations in the levels of cariogenic organisms and saliva secretion rate of patients (n = 30) with bulima nervosa. Profile analysis suggested that, over the course of the study, binging and purging frequency and Streptococcus sobrinus salivary levels decreased significantly in the fluoxetine group as compared with the placebo group. Our finding that S. sobrinus levels decreased 16 weeks after subjects were on medication suggests that the salivary levels of these organisms could serve as an objectively measured indicator of patient compliance with antibulimic therapy.

Analysis of Variance↗

PubMed1993

The use of a rapid enzymatic assay in the field for the detection of infections associated with adult periodontitis.

There are few objective assays for studies of the epidemiology of periodontal diseases. The PerioScan is an assay capable of detecting three periodontal pathogens, namely T. denticola, P. gingivalis, and B. forsythus, which have been associated with adult periodontitis. The PerioScan was tested in a sample of 301 Brazilians. Clinical indices--bleeding, probing depth, gingival index, and periodontal index--were recorded from four sites in each subject. Subgingival plaque samples were collected from those sites and placed on the PerioScan card. Color results were scored in the field after 15 minutes. The plaque samples were screened with polyclonal antibodies for the three species by an ELISA system. The PerioScan, when compared with the ELISA system, yields a sensitivity of 91 percent, specificity of 89 percent, and an accuracy of 90 percent. When the PerioScan was compared to clinical indices, there was a high sensitivity (at least 93%) and a low specificity (no less than 47%), with an accuracy of at least 61 percent.

Adolescent↗

PubMed1992

Effect of home blood pressure and gender on estimates of the familial aggregation of blood pressure. The Tecumseh Blood Pressure Study.

Blood pressure (BP) readings from a single clinic visit are often used in population studies investigating the genetic basis of BP. We examined first-degree relatives in the Tecumseh Blood Pressure study to compare heritability estimates of BP readings obtained in the clinic-office setting (the average of two seated readings) with self-reported home BP readings (the average of 14 readings) taken over a 1-week period. The hypothesis tested was that repeated BP readings obtained in the home over the 1-week period would have fewer artifacts (i.e., environmentally induced variability in BP) and thus would better estimate the true "basal" BP that, in turn, would improve heritability estimates. We and others assume that the true basal BP level is heritable. We therefore expected that this "true" BP, by reducing BP variability of offspring, would show a stronger between-sibling correlation and that it would correlate better to parental BP as measured in a clinic setting. Correlation coefficients were calculated between siblings in the present Tecumseh study using self-reported home BP and clinic BP readings. Among 380 siblings (average age, 31.4 years), correlation coefficients for the home readings were of the same magnitude as for office readings (home, r = 0.23, p less than 0.01; office, r = 0.24, p less than 0.01). When offspring clinic BP readings were compared with archived BP data on parents, the correlation between offspring clinic and parental clinic BP readings was stronger (r = 0.24, p less than 0.05) than the correlation of offspring home BP readings to parental clinic BP readings (r = 0.17, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Correlates of the estimated arterial compliance in the population of Tecumseh, Michigan.

An estimate of arterial compliance--the stroke volume/pulse pressure ratio (SV/PP)--was studied in 801 participants in the Tecumseh Blood Pressure Study, a population-based ongoing cardiovascular, epidemiological investigation. The subjects were normal young adults (mean age 30 +/- 5.6 years) and 373 were females. Cardiac anatomy and function were studied by echo-Doppler methods, blood pressure being measured at the same time by the indirect method. The distribution of the SV/PP ratio was skewed toward higher values in larger subjects. After statistical adjustments for body surface area, this estimate of arterial compliance was found to be higher in females (2.00 +/- 0.62) than in males (1.90 +/- 0.58) (p < 0.05). When subjects were divided into tertiles, the group with the lowest estimated arterial compliance was normotensive but had higher systolic pressure, lower diastolic pressure, a similar mean arterial pressure, higher heart rate and higher left ventricular wall thickness ratio compared to subjects with higher arterial compliance. Indices of systolic ejection decreased and diastolic function was altered in the low compliance subjects. In addition, low compliance subjects also had higher fasting insulin levels. These findings suggest that the low arterial compliance in an otherwise normal population has negative cardiovascular correlates. The early association of decreased arterial compliance with anatomic, functional and biochemical aberrations suggests that estimates of arterial compliance might prove useful for prediction of cardiovascular complications.

Adolescent↗

PubMed1992

White coat hypertension: a follow-up.

Home blood pressure readings by self-monitoring (14 readings in 7 days) have been compared to readings taken in the clinic in 937 participants of the Tecumseh Blood Pressure Study. In the absence of firm criteria "hypertension at home" was defined as having home readings in the upper decile of the whole population. If a clinic reading exceeded 140 and/or 90 mmHg a subject was categorized as having clinic "hypertension". Two hypertensive groups emerged; one with both clinic and home hypertension ("sustained" N = 47) and one with high clinic but normal home blood pressure ("white coat" N = 50). Groups with "white coat" and "sustained" hypertension were very similar. Both groups were overweight, had faster heart rates, elevated cholesterol, insulin, triglyceride and decreased HDL levels. Blood pressure readings at previous exams (age 5, 8, 21 and 22) were elevated in both the "sustained" and white coat hypertension group compared to the normotensive controls. Subjects with white coat hypertension were not hyperresponders to the stress of mental arrythmetrics or to isometric exercise. The white coat hypertensives did not show abnormal anger, excessive submissiveness, or anxiety. The pathophysiology of the reproducible elevation of the clinic blood pressure in the white coat hypertensives remains unclear. Because of a higher risk of coronary heart disease and a risk for late development of sustained hypertension, subjects with white coat hypertension should be counselled on nonpharmacologic methods to control the blood pressure elevation and to ameliorate coronary risk factors.

Adolescent↗

PubMed1991

Efficient computation of patterned covariance matrix mixed models in quantitative segregation analysis.

The use of patterned covariance matrices in forming pedigree-based mixed models for quantitative traits is discussed. It is suggested that patterned covariance matrix models provide intuitive, theoretically appealing, and flexible genetic modeling devices for pedigree data. It is suggested further that the very great computational burden assumed in the implementation of covariance matrix-dependent mixed models can be overcome through the use of recent architectural breakthroughs in computing machinery. A brief and nontechnical overview of these architectures is offered, as are numerical and timing studies on various aspects of their use in evaluating mixed models. As the kinds of computers discussed in this paper are becoming more prevalent and easier to access and use, it is emphasized that it behooves geneticists to consider their use to combat needless approximation and time constraints necessitated by smaller, scalar computation oriented, machines.

Algorithms↗

PubMed1991

Independence of pressure reactivity from pressure levels in Tecumseh, Michigan.

The relation between blood pressure level and reactivity to mental arithmetic and isometric exercise was investigated in 169 men and 120 women (average age, 32.3 years) from the village of Tecumseh, Mich. In the entire population, the correlation between baseline blood pressure and blood pressure response to both stressors was not significant. Blood pressure reactivity to both stressors was not increased in participants with borderline hypertension (one clinic reading of more than 140 mm Hg systolic and/or 90 mm Hg diastolic). When subjects were classified according to blood pressure response (below and above the 80th percentile), the hyperreactors to mental and physical stress had normal baseline blood pressure values. The hyperreactors also had clinic-to-home blood pressure differences similar to those of the rest of the population. Participants who had borderline hypertension at age 32 years had significantly elevated blood pressures at ages 5, 8, 12, 21, and 22 years. Those who were hyperreactors at age 32 years had normal blood pressures as children and young adults. Results of the present study lend no support to an association between higher blood pressures and blood pressure hyperreactivity. Study participants in Tecumseh will be recalled for future examinations. The independence of blood pressure levels from blood pressure reactivity offers a unique opportunity to prospectively evaluate their separate effects on cardiovascular morbidity.

Adolescent↗

PubMed1990

The association of borderline hypertension with target organ changes and higher coronary risk. Tecumseh Blood Pressure study.

The Tecumseh project investigates the evolution of hypertension in a healthy population. Of 946 subjects aged 18 through 38 years, 124 had clinic blood pressure readings higher than 140/90 mm Hg (the mean for borderline hypertensive subjects was 130/94 mm Hg). Compared with normotensive subjects, borderline hypertensive subjects had higher home blood pressures (mean, 12/7 mm Hg higher). Their childhood and postpubertal blood pressures were elevated (6/4 mm Hg higher than normal at age 6 years and 12/7 mm Hg higher than normal at age 21 years), and hypertensive target organ changes were detected. Borderline hypertensive subjects also had elevated minimal forearm resistance (0.22 U higher than normal), decreased stroke index (1.8 mL/m2 lower than normal), and impaired ventricular diastolic relaxation (mitral Doppler peak early diastolic blood flow [E] to peak late diastolic blood flow [A] ratio 0.13 lower than normal). Borderline hypertensive subjects had significant abnormalities in other coronary risk factors (cholesterol levels were 0.39 mmol/L higher, triglyceride levels were 0.45 mmol/L higher, high-density lipoprotein levels were 0.08 mmol/L lower, insulin levels were 38 pmol/L higher, and 16.5% more of them were overweight). Borderline hypertension is neither transient nor innocuous. Its association with other predictors of atherosclerosis calls for clinical attention.

Adolescent↗

PubMed1990

"White coat" versus "sustained" borderline hypertension in Tecumseh, Michigan.

During a survey of young subjects not receiving treatment for hypertension in Tecumseh, Michigan, clinic and self-monitored blood pressures taken at home (14 readings in 7 days) were obtained in 737 subjects (387 men, 350 women, average age 31.5 years). Hypertension in the clinic was diagnosed if the clinic blood pressure exceeded 140 mm Hg systolic or 90 mm Hg diastolic. In the absence of firm criteria for what constitutes hypertension at home, subjects whose average home blood pressure was in the upper decile of the whole population were considered to have hypertension at home. By these criteria, 7.1% of the whole population had "white coat" hypertension (i.e., high clinic but not elevated home readings). The prevalence of "sustained" hypertension (i.e., high readings in the clinic and at home) was 5.1%. Subjects with white coat and sustained borderline hypertension in Tecumseh were very similar. Both groups showed, at previous examinations (at ages 5, 8, 21, and 23 years), significantly higher blood pressure readings than the normotensive subjects. As young adults (average age 33.3 years), the parents of both hypertensive groups had significantly higher blood pressure readings than the parents of normotensive subjects. Both hypertensive groups had faster heart rates, higher systemic vascular resistance, and higher minimal forearm vascular resistance. Both hypertensive groups were more overweight, had higher plasma triglycerides, insulin, and insulin/glucose ratios than normotensive subjects. The white coat hypertensive group also had lower values of high density lipoprotein than the normotensive group. White coat hypertension is a frequent condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Predictors of blood pressure and hypertension in Tecumseh, Michigan.

Correlates of present blood pressure status are analyzed in 576 subjects (271 males, average age 32 years) in Tecumseh, Michigan. In addition to the current values, anthropometric and blood pressure data are available when the subjects were, on average, 6.9 and 22.2 years of age. Data on 351 fathers and 368 mothers when they were, on average, 32 years old are also available. Moderate, but significant correlations were found between present and past blood pressure and between past weight or skinfold thickness and the present blood pressure. These correlations were much weaker for childhood values than for values at age 22. When multiple regression techniques were used with blood pressure values at age 22 and parental values as independent variables, 40% of the present systolic blood pressure variance could be explained. Prediction of present hypertension status (blood pressure greater than 140 and/or 90 mm Hg) was evaluated by discriminant analysis. Three variables (weight at age 22, systolic blood pressure at age 22, and father's diastolic blood pressure) entered the model and accurately predicted the present blood pressure classification in 89% of the sample. When current blood pressure status was assessed with respect to previous blood pressure classification (upper 20%), family background, and overweight, a gradient of risk for hypertension was found. On the low end of risk was high childhood pressure (risk 19.1% versus 12.1% in the overall population). The highest risk occurred for those with high pressure and overweight at 22 years who also had a family background of high blood pressure (44% versus 12.1%). The prediction of hypertension from young adulthood to the early fourth decade of life is feasible and permits delineation of populations targeted for primary prevention.

Adult↗

PubMed1989

Testing separate families of segregation hypotheses: bootstrap methods.

Aspects of the statistical modeling and assessment of hypotheses concerning quantitative traits in genetics research are discussed. It is suggested that a traditional approach to such modeling and hypothesis testing, whereby competing models are "nested" in an effort to simplify their probabilistic assessment, can be complimented by an alternative statistical paradigm - the separate-families-of-hypotheses approach to segregation analysis. Two bootstrap-based methods are described that allow testing of any two, possibly non-nested, parametric genetic hypotheses. These procedures utilize a strategy in which the unknown distribution of a likelihood ratio-based test statistic is simulated, thereby allowing the estimation of critical values for the test statistic. Though the focus of this paper concerns quantitative traits, the strategies described can be applied to qualitative traits as well. The conceptual advantages and computational ease of these strategies are discussed, and their significance levels and power are examined through Monte Carlo experimentation. It is concluded that the separate-families-of-hypotheses approach, when carried out with the methods described in this paper, not only possesses some favorable statistical properties but also is well suited for genetic segregation analysis.

Alleles↗