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Biomedical subjects

J C Christian

Publications and source records attributed to J C Christian.

At least 73 records · Page 4Linked to original sources

Twin study: relationship between birth weight, zygosity, placentation, and pathologic placental changes.

We examined the placentas of 182 like-sexed live-born twins: 73 placentas (40.1%) were monochorionic and 109 (59.9%) were dichorionic. All twin pairs with monochorionic placentas were monozygotic (MZ), but 28.9% of pairs with dichorionic placentas were MZ. Analysis of birth weights demonstrated that dichorionic and dizygotic (DZ) twins were heaviest, and suggested that the chorion status is a more important determinant of birth weight than zygosity. Vascular anastomoses were identified only in monochorionic placentas and occurred in 79.5% of cases. All placentas with deep anastomoses had superficial anastomoses. A higher proportion of velamentous and marginal insertions of the umbilical cord in monochorionic placentas (27.4%) compared to dichorionic placentas (13.8%) supports the belief that lateral placental growth is greatest in twin gestations in which the embryos are initially most closely apposed--The theory of trophotropism.

Birth Weight↗

Nutrient intake and blood pressure: families of adult identical twins.

To investigate the relationship of dietary intake to blood pressure, 198 adults and 53 children who were members of 92 nuclear families completed a 3-day diet diary prior to an outpatient clinic examination for cardiovascular disease risk factors. Nutrient intake was significantly related to age and anthropometric variables in adults. Sodium and potassium intake were related to blood pressure in adults, but this relationship was no longer significant after adjustment for caloric intake. The diet and blood pressure relationships in children were less clear. Multiple linear regression techniques using age, anthropometric variables, and nutrient intake demonstrated that in adults age and skinfold were the principal determinants of blood pressure, but in children age and saturated fat intake were most likely to enter the equations. In comparisons of normotensive and hypertensive adults, there were no differences in the dietary intakes of these electrolytes. The results of this investigation underscore the complex interaction of nutrient intake with body size and age. Investigators who focus only on a few nutrients and fail to account for other sources of variation can be misled.

Adult↗

Blood pressure response to dietary sodium restriction in healthy normotensive children.

To examine the effect of dietary sodium restriction on blood pressure, 149 healthy, normotensive children (64 males, 85 females) participated in a study designed to lower Na intake and maintain Na excretion at less than or equal to 75 mmol/d or half usual intake for 12 wk. Na excretion was decreased during the study period in both males (112.9 +/- 6.3 vs 53.4 +/- 3.6 mmol, p less than 0.001) and females (91.1 +/- 3.2 vs 41.1 +/- 1.9 mmol, p less than 0.001). Changes in systolic blood pressure were not significant in either sex but females showed a decrease (p less than 0.05) in diastolic and mean arterial blood pressures. Because blood pressure in children is correlated with age and body size, multiple linear regression was used to adjust blood pressure levels for age and weight. These analyses yielded small but significant decreases in systolic, diastolic, and mean arterial pressure measurements. The blood pressure response was heterogeneous but this variable response could not be attributed to varying degrees of compliance within families. These results suggest that compliance with modest Na restriction does not consistently lower blood pressure in normotensive children.

Blood Pressure↗

Genetic influences on the response to dietary salt reduction, acute salt loading, or salt depletion in humans.

The effect of heredity on blood pressure is established. However, not all genetically predisposed individuals develop an elevated blood pressure. Thus, an environmental factor may also be required for expression of this genetic predisposition. To elucidate this effect further, as well as to examine the relationship between inherited factors and the influence of salt intake, we conducted acute and chronic investigations in normal subjects. We present evidence that renal function, the renin-angiotensin-aldosterone system, and sympathetic nervous system are all influenced by genetic variance. We found that the blood pressure response to both acute changes in volume and changes in salt intake is normally distributed, supporting the notion of salt sensitivity and resistance of blood pressure. We identified phenotypes of haptoglobin as possibly useful indicators of salt sensitivity and resistance. We documented a parent-offspring resemblance in blood pressure and also a maternal-offspring resemblance in the change in blood pressure with salt reduction. We present evidence that suggests that salt-sensitive persons exhibit differences in renin-aldosterone relationships and natriuretic responses consistent with volume expansion compared to salt-resistant individuals. Finally, we identified a potential role for altered adrenoreceptors in the development of salt sensitivity. Our observations speak to the inherited nature of salt sensitivity and resistance of blood pressure. They may have mechanistic implications as well.

Diet, Sodium-Restricted↗

Influence of genetic variance on sodium sensitivity of blood pressure.

To examine the effect of genetic variance on blood pressure, sodium homeostasis, and its regulatory determinants, we studied 37 pairs of monozygotic twins and 18 pairs of dizygotic twins under conditions of volume expansion and contraction. We found that, in addition to blood pressure and body size, sodium excretion in response to provocative maneuvers, glomerular filtration rate, the renin-angiotensin system, and the sympathetic nervous system are influenced by genetic variance. To elucidate the interaction of genetic factors and an environmental influence, namely, salt intake, we restricted dietary sodium in 44 families of twin children. In addition to a modest decrease in blood pressure, we found heterogeneous responses in blood pressure indicative of sodium sensitivity and resistance which were normally distributed. Strong parent-offspring resemblances were found in baseline blood pressures which persisted when adjustments were made for age and weight. Further, mother-offspring resemblances were observed in the change in blood pressure with sodium restriction. We conclude that the control of sodium homeostasis is heritable and that the change in blood pressure with sodium restriction is familial as well. These data speak to the interaction between the genetic susceptibility to hypertension and environmental influences which may result in its expression.

Adolescent↗

Plasma cholesterol variation in the National Heart, Lung and Blood Institute Twin Study.

Plasma cholesterol was measured in the fifth decade of the life of 249 pairs of monozygotic (MZ) and 262 pairs of dizygotic (DZ) World War II veteran twins and 70% of the same cohort 10 years later. There were no significant differences between the mean cholesterol values for MZ and DZ twins, and the within DZ pair mean squares were significantly larger than the within MZ pair mean squares for all of the cholesterol variables measured. However, the DZ twins were found to have greater total variance, positive skewness, and leptokurtosis than the MZ twins for total and high-density lipoprotein cholesterol, and the total/high-density ratio. Comparisons with published data revealed that the variance of DZ twins was similar to that of singletons while the MZ twins have smaller total variance, perhaps owing to a missing component of variation. Hypotheses for the source of the differences in the zygosity distributions are proposed including environmental influences (pre- or post-natal and within- or among-families), genetic differences, and selection at the time of induction into the armed services. Because of the differences in total variance of the two zygosities it is difficult to know which estimates of genetic variance or heritability have the least bias. However, these data provide clues that may lead to further understanding of sources of plasma cholesterol variation that could be important to the future understanding of risk for coronary heart disease.

Cholesterol↗

Localization of the gene for a syndrome of X-linked skeletal dysplasia and mental retardation to Xq27-qter.

An Indiana family segregating a syndrome of X-linked mental retardation and skeletal anomalies was tested for linkage of the mutant gene to X-chromosome molecular markers. Lod scores of 3.27 and 3.06 (theta = 0) for the molecular probes St14-1 (DXS52) and Dx13 (DXS15), respectively, indicate that the disease gene is located in the terminal portion of Xq.

Bone Diseases, Developmental↗

Heterogeneity of blood pressure response to dietary sodium restriction in normotensive adults.

To investigate the effect of dietary sodium restriction on blood pressure in healthy, normotensive adults, 82 individuals (36 men, 46 women) participated in a study of restricted sodium intake (less than or equal to 75 mEq/day) for a period of 12 weeks. For the entire population there was a small but significant (p less than 0.01) decrease in mean arterial pressure during sodium restriction. The change in blood pressure was significantly correlated with age (r = 0.23, p less than 0.05). Division of the population at age 40, showed that the older individuals were more likely to have a decreased blood pressure during sodium restriction, while as a group younger adults showed no change. The individual blood pressure responses were heterogeneous with increases in pressure observed in some subjects. These results suggest that "sodium sensitivity" of blood pressure may be more evident with increasing age. Further, sodium restriction in all normotensive adults may not be innocuous.

Adult↗

Familial resemblance in the blood pressure response to sodium restriction.

Familial resemblance in the blood pressure response to sodium restriction in normotensive persons was investigated. Forty-four families of identical twin children participated in a sodium restriction (less than or equal to 75 meq/day) protocol for a period of 12 weeks. Subjects were residents of central Indiana, and the study was conducted over a three-year period. Parent-offspring and sibling-sibling resemblances for actual blood pressure were not different under conditions of ad lib sodium intake versus sodium restriction. Mother-offspring resemblance in blood pressure change with sodium restriction was significant for systolic (p less than 0.001), diastolic (p less than 0.05), and mean arterial (p less than 0.05) pressures. Sibling-sibling and twin-twin resemblances were also highly significant for the change in all three blood pressures. Father-offspring resemblances were marginal (p less than 0.10). This study is, to the author's knowledge, the first to demonstrate significant familial resemblances in blood pressure change with sodium restriction in normotensive persons.

Adolescent↗

Blood pressure response to potassium supplementation in normotensive adults and children.

To investigate the effect on blood pressure of a modest increase in dietary potassium intake, 38 healthy, free-living families were enrolled in a study involving 4 weeks of potassium supplementation. This was preceded by collection of five baseline measurements of blood pressure and urinary electrolyte excretion and followed by a 4-week recovery period. Although there was a significant increase in urinary potassium excretion during supplementation in both adults and children (p less than 0.001), there were no significant changes in systolic, diastolic, or mean arterial blood pressure. Height and weight increased significantly in children (p less than 0.001), and weight increased in adults (p less than 0.01) over the course of the study. Multivariate analysis of variance of blood pressure controlling for these confounding variables failed to reveal any effect of the potassium supplementation on blood pressure. These results suggest that increasing intake of dietary potassium alone in a healthy, free-living normotensive population is unlikely to have a discernible effect on blood pressure.

Adolescent↗

Association of haptoglobin with sodium sensitivity and resistance of blood pressure.

Sodium sensitivity and resistance of blood pressure were examined in 117 normotensive and 85 hypertensive subjects by means of a protocol using rapid extracellular fluid volume expansion with intravenously administered saline (2 L over 4 hours) followed by a day of low dietary sodium intake (10 mEq) and volume contraction induced by a diuretic (furosemide, 120 mg orally). Genetic markers were also examined. Both hypertensive and normotensive subjects with haptoglobin 1-1 phenotype were significantly more (p less than 0.05) likely to be sodium-sensitive than were those with 2-1 or 2-2 phenotypes, and subjects with 2-2 phenotypes were more apt to be sodium-resistant. A second population was examined in which both adults and children with haptoglobin 1-1 phenotype were found to have significantly (p less than 0.05) higher casual systolic and diastolic blood pressures. These two studies independently confirm a relationship between haptoglobin phenotypes and blood pressure and suggest an environmental factor (sodium) as well.

Adolescent↗

Genetic, familial and racial influences on blood pressure control systems in man.

This paper reviews investigations by the Indiana University Medical Centre Hypertension Research Centre into genetic influences on blood pressure control systems in man. Our studies have used the families of adult identical twins to partition the relationships of age, sex and body size to the genetic contribution to blood pressure variability. These studies provide little evidence for environmental influence on the familial aggregation of blood pressure and suggest that at least 63% of the variability is due to genetic factors. Studies on the renin-angiotensin-aldosterone system and on the kidney's ability to excrete sodium were also undertaken in identical and fraternal twins, as well as in black and white subjects, and provided unequivocal evidence of genetic control. Studies in first degree relatives of patients with essential hypertension have demonstrated higher plasma renin levels and a decreased ability to excrete a sodium load when compared to first degree relatives of normotensive subjects. Blacks in the U.S.A. have a decreased ability to excrete a sodium load and a greater rise in blood pressure with sodium loading than do whites. We suggest that the heritability of blood pressure is directly related to a genetic influence on the level of renin and that this increase in renin level results in subtle increases in angiotensin II. These chronic elevations of angiotensin II directly increase blood pressure and decrease the kidney's ability to excrete sodium by either a direct renal effect or indirectly by stimulating aldosterone-dependent sodium retention.

Adult↗

Estimation of dietary sodium intake in children.

To examine the utility of nocturnal urine collections in the estimation of dietary sodium intake in children, 29 families who agreed to lower their dietary sodium intake to less than 65 mEq/d were studied. A total of 58 adults and 95 children collected urine specimens weekly or biweekly before and after being instructed in a dietary sodium restriction regimen. Urine collections were fractionated into a diurnal and nocturnal portion. Sodium was measured directly, and estimated by measuring chloride excretion with a chloride titrator stick. Nocturnal chloride and 24-hour sodium excretion were highly correlated in adults (r = .75), and slightly less so (r = .56) in children. The slopes of the relationships were not different. Discriminant analysis showed that two or more chloride estimates permitted classification of both adults and children into the low sodium intake category with 100% accuracy, and into the normal sodium intake category with 75% accuracy. It was concluded that nocturnal chloride estimates are as useful in estimating compliance to a reduced sodium intake in children as in adults.

Adolescent↗

Birth weight and placental proximity in like-sexed twins.

In addition to zygosity, the type of placentation has proven to be an important variable in twin studies. A number of quantitative traits in human twins have been found to be influenced by chorion type. Our study confirms an earlier finding that there is larger within-pair birth weight variability in dichorionic twins with fused placentas than in those with separate placentas. This finding emphasizes the importance of detailed twin placental examinations to help identify traits that may be influenced by prenatal environmental influences.

Analysis of Variance↗

A search for stratification-free association between plasma lipids and HLA using dizygotic twins.

A total of 71 pairs of like-sexed dizygotic twins were studied, comparing within-pair differences for plasma total, free and esterified cholesterol, and triglyceride with the number of HLA haplotypes the twins had in common. If associations are present between HLA and the blood lipids studied, the twins with no haplotypes in common would be expected to have the largest within-pair mean square, those with two in common the smallest, and those with one in common an intermediate value. No significant differences were found comparing within- pair mean squares for the variables studied.

Adolescent↗

Use of twins to study environmental effects.

Extrapolation from pharmacogenetic studies would indicate that there is a great deal of genetic variability in the response of humans to noxious environmental agents. Co-twins provide the most closely matched genetic controls possible and, in addition, are matched perfectly for age and often have shared very similar environments since before birth. The efficiency of co-twin control studies can be further increased by the use of sequential analysis, so that for the studies of the effects of environmental agents on human populations, twins would give answers that would require many more unrelated subjects. Use of twins in epidemiology studies is now in its infancy, but investigators should carefully consider the use of this powerful experimental tool and begin to identify twins in population surveys.

Analysis of Variance↗

Genetic aspects of the blood pressure control system.

Utilization of several genetic models (twins, families of monozygotic twins, characterized hypertensives and normotensive first-degree-relatives of essential hypertensives) has permitted us to probe for evidence of genetic mediation of several components of the blood pressure control system in humans. These studies have identified evidence for genetic mediation of systolic blood pressure in a cross-sectional study of normotensive subjects covering a wide age span. Further, this effect was independent of body size. The twin model, studied under conditions of sodium loading and sodium and volume depletion, demonstrated a genetic component in the response of plasma renin activity, aldosterone, norepinephrine and renal sodium excretion to these maneuvers. Among hypertensive subjects and unexpected abnormality in the distribution of a specific MNS blood group pattern was seen in renal vascular hypertensives. This may provide a new genetic marker for identifying individuals at increased risk to develop this abnormality.

Blood Pressure↗

Application of the major gene index and offspring-between-parents function to dermatoglyphic fingertip variables.

Forty-eight digital dermatoglyphic variables in 192 nuclear families were analyzed to search for evidence of major gene effects, utilizing a pair of recently developed statistics called the major gene index (MGI) and offspring-between-parents (OBP) function. They operate on the principle that under a multifactorial blending inheritance scheme an offspring's phenotypic value approximates the midparental value, whereas under major gene inheritance, the child's value more closely resembles that of one of his parents. Both statistics yielded comparable results. All ridge-count variables showed no strong deviation from a multifactorial model. Pattern-type variables gave values suggesting the presence of major gene effects, but these results were probably the consequence of the variables' relatively discrete distributions, since a departure of a variable from a reasonably continuous phenotypic distribution was shown to interfere significantly with the interpretation of both statistics.

Chromosome Mapping↗