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Biomedical subjects

J C Christian

Publications and source records attributed to J C Christian.

At least 19 recordsLinked to original sources
PubMed1992

Long-term bone loss in men: effects of genetic and environmental factors.

OBJECTIVE: To identify environmental factors associated with bone loss in adult male twins and to determine the extent to which shared environmental characteristics affect estimates of the genetic influence on bone loss. DESIGN: A 16-year cohort study. SETTING: A midwestern university hospital. PARTICIPANTS: One hundred and eleven male veterans of World War II or the Korean conflict, born between 1916 and 1927. All were twins, with the sample comprising 48 pairs and 15 persons whose twin brothers were deceased or seriously ill. MEASUREMENTS: Bone mass and environmental characteristics (cigarette smoking, alcohol consumption, physical activity, dietary calcium intake, use of thiazide diuretics) measured at baseline and 16 years later. RESULTS: Rates of radial bone loss averaged 0.45% per year. Those who both smoked and used alcohol at levels greater than the median for the population had a rate of bone loss (10% in 16 years) twice the rate of those who were below the median level for both variables (5% bone loss, P = 0.003). Rates of bone loss were correlated within twin pairs, and these correlations were diminished 25% to 35% by adjustments for environmental influences on bone loss. However, statistically significant within-pair correlations remained (r = 0.4), which did not differ between monozygotic and dizygotic twin pairs after adjustments for smoking, alcohol use, dietary calcium intake, and exercise. CONCLUSIONS: Bone loss in men during mid-life is determined, at least in part, by environmental factors, including smoking, alcohol intake, and, possibly, physical activity. Rates of bone loss were similar within twin pairs, apparently because of a shared environment.

Alcohol Drinking↗
PubMed1992

Calcium supplementation and increases in bone mineral density in children.

BACKGROUND: Increased dietary intake of calcium during childhood, usually as calcium in milk, is associated with increased bone mass in adulthood; the increase in mass is important in modifying the later risk of fracture. Whether the increase is due to the calcium content of milk, however, is not certain. METHODS: We conducted a three-year, double-blind, placebo-controlled trial of the effect of calcium supplementation (1000 mg of calcium citrate malate per day) on bone mineral density in 70 pairs of identical twins (mean [+/- SD] age, 10 +/- 2 years; range, 6 to 14). In each pair, one twin served as a control for the other; 45 pairs completed the study. Bone mineral density was measured by photon absorptiometry at two sites in the radius (at base line, six months, and one, two, and three years) and at three sites in the hip and in the spine (at base line and three years). RESULTS: The mean daily calcium intake of the twins given placebo was 908 mg, and that of the twins given calcium supplements was 1612 mg (894 mg from the diet and 718 mg from the supplement). Among the 22 twin pairs who were prepubertal throughout the study, the twins given supplements had significantly greater increases in bone mineral density at both radial sites (mean difference in the increase in bone mineral density: midshaft radius, 5.1 percent [95 percent confidence interval, 1.5 to 8.7 percent]; distal radius, 3.8 percent [95 percent confidence interval, 1.4 to 6.2 percent]) and in the lumbar spine (increase, 2.8 percent [95 percent confidence interval, 1.1 to 4.5 percent]) after three years; the differences in the increases at two of three femoral sites approached significance (Ward's triangle in the femoral neck, 2.9 percent; greater trochanter, 3.5 percent). Among the 23 pairs who went through puberty or were postpubertal, the twins given supplements received no benefit. CONCLUSIONS: In prepubertal children whose average dietary intake of calcium approximated the recommended dietary allowance, calcium supplementation increased the rate of increase in bone mineral density. If the gain persists, peak bone density should be increased and the risk of fracture reduced.

Absorptiometry, Photon↗
PubMed1992

Plots for examination of univariate twin data.

We discuss informative plots for univariate twin data that can be used in conjunction with twin data analyses. The plots are useful for spotting outliers, spotting possible single gene effects, and displaying the contribution of individual twin pairs to the fit of genetic models of the data. We illustrate the use of the plots on bone mineral data, and present programs for generating the plots in SAS.

Data Interpretation, Statistical↗
PubMed1992

TWINAN90: a FORTRAN program for conducting ANOVA-based and likelihood-based analyses of twin data.

We discuss the program, TWINAN90, which can perform several different types of analysis of twin data. TWINAN90 incorporates the ANOVA-based twin analyses from the TWINAN twin analysis program, and also includes maximum likelihood estimation of parameters from three path models. Another feature of TWINAN90 is the optional output of a pedigree file which can be read by the quantitative genetics package FISHER. The diagnostic features of the program make TWINAN90 useful also for preliminary analyses prior to the use of more sophisticated modeling procedures which are available in packages such as LISREL and FISHER. An annotated printout from TWINAN90 is presented to illustrate the statistical analyses performed in the program.

Analysis of Variance↗
PubMed1991

Concordance for dyslipidemic hypertension in male twins.

Sixty cases of dyslipidemic hypertension were identified in the 1028 middle-aged, white, male twin participants in the first examination of the National Heart, Lung, and Blood Institute Twin Study (1969 to 1973). The prevalence of dyslipidemic hypertension was similar by zygosity but proband concordance was three times greater in monozygotic than dizygotic twins (0.44 [seven concordant and 18 discordant pairs] vs 0.14 [two concordant and 24 discordant pairs]), suggesting a genetic effect on the condition. Low high-density lipoprotein cholesterol level was the most common lipid abnormality in concordant pairs. Mortality from ischemic heart disease was significantly higher in individuals with dyslipidemic hypertension. Obesity and glucose intolerance were closely associated with the syndrome. Moreover, within the 18 discordant monozygotic twin pairs, the twins with dyslipidemic hypertension had gained significantly more weight as adults and were significantly heavier than their unaffected cotwins. Thus, although genetic factors may influence development of dyslipidemic hypertension, nongenetic, potentially modifiable aspects of obesity are also closely related to expression of this clinically important syndrome.

Adult↗
PubMed1991

Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates.

We estimated genetic effects on bone density in pre- and postmenopausal twins and critically considered the assumptions of the twin model. Bone mass in the radius, lumbar spine, and hip, anthropometric measurements, usual calcium and caffeine intake, tobacco and alcohol use, number of pregnancies and live births, menstrual history, usual physical activity, and medical history were measured in a volunteer sample of 171 twin pairs [124 monozygotic (MZ) and 47 dizygotic (DZ)], aged 25-80, free of diseases known to affect bone mass or mineral metabolism. At all skeletal sites, MZ intraclass correlations exceeded DZ correlations for both pre- and postmenopausal women, yielding highly significant estimates of heritability for bone mass. Adjustments for height, age, and environmental characteristics did not reduce the heritability estimates. However, many of these estimates were unrealistically high, suggesting some violation(s) of the assumptions of the twin model. Thus, the familial resemblance in bone mass is due primarily to genetic effects at all skeletal sites and at all ages, although the importance of genetic effects is diminished with aging, as evidenced by increasing within-MZ pair variability in older women. Because of failures in the assumptions of the twin model, however, particularly the greater MZ environmental similarity and the probability of gene interaction, heritability estimates are probably too high and require cautious interpretation.

Adult↗
PubMed1991

No evidence for an effect of lactase deficiency on bone mass in pre- or postmenopausal women.

The potential role for lactase deficiency in the development of low bone mass was examined in 342 adult female twins. Diminished lactase activity, defined as greater than 20 ppm increase in expired hydrogen at 2 or 2.5 h after an oral lactose load, was examined: (1) by comparing bone mass between members of twin pairs discordant for lactase activity; (2) by examining the linear association between bone mass and total expired hydrogen gas; and (3) by comparing all lactase-deficient individuals to those with persistent lactase activity. Among members of discordant (primarily DZ) pairs, the lactase-deficient member had greater bone mass 54% of the time. The correlations between the increase in expired hydrogen and bone mass at various sites were between -0.02 (femoral neck) and 0.11 (midshaft radius), suggesting no association between these variables. Finally, all lactase-deficient subjects were compared with those with normal lactase activity, regardless of twin status, and at each skeletal site the differences in bone mass were 1% or less. Thus, all primary hypotheses were not supported by these data; that is, in this large sample we could find no evidence of a detrimental effect of lactase deficiency on adult bone mass. However, baseline expired hydrogen was consistently and positively associated with bone mass at all sites, independently of age, suggesting the possibility that some aspect of intestinal function related to the activity of bacterial anaerobes may be positively associated with bone mass.

Absorptiometry, Photon↗
PubMed1991

The NHLBI Twin Study: heritability of apolipoprotein A-I, B, and low density lipoprotein subclasses and concordance for lipoprotein(a).

Heritability of plasma apolipoprotein (apo) A-I, apo B, and low density lipoprotein (LDL) subclasses and concordance for lipoprotein(a) excess were assessed in 109 monozygotic (MZ) and 113 dizygotic (DZ) twin pairs participating in the third examination of the National Heart, Lung, and Blood Institute Twin Study. The intraclass correlation coefficient for apo A-I was significantly greater in MZ twins (0.56) than in DZ twins (0.37, P less than 0.05); however, apo A-I showed an unequal distribution in the two groups, with significantly greater total variance in DZ twins. Therefore the among-component estimate of genetic variance was applied, and the results indicated no significant heritability for apo A-I (P = 0.59). MZ and DZ twins had equal apo B variance. The intraclass correlation coefficient for apo B in MZ twins (0.71) was significantly higher than in DZ twins (0.25) (P less than 0.0001), indicating significant heritability for apo B. Plasma apo A-I levels were significantly correlated with alcohol intake (P less than 0.0001), body mass index (BMI, P less than 0.0001), and physical activity, while apo B levels were significantly correlated only with BMI (P less than 0.05). After plasma apo A-I and apo B concentrations were adjusted for all of these variables and for cigarette smoking, the analysis of variance and intraclass correlation coefficients remained virtually unchanged. The LDL type intraclass correlation coefficient was higher in MZ twins (0.58) than in DZ twins (0.32, P less than 0.005); however, greater total variance for this parameter in DZ twins was observed and after applying the among component estimate of genetic variance, no significant heritability of LDL type was observed. After adjustment for covariate effects the conclusions were not changed. Only 8.4% of MZ twin pairs, as compared with 26.7% of DZ twin pairs, were discordant for elevated lipoprotein(a) on gradient gels (P less than 0.0001). Our data indicate that there is a strong heritability for plasma apo B and lipoprotein(a), with only weak evidence for heritability of LDL type or plasma apo A-I levels within this population sample.

Aged↗
PubMed1991

Concordance of ischemic heart disease in the NHLBI twin study after 14-18 years of follow-up.

Morbidity and mortality were assessed in the NHLBI twin study at the end of 1987. Deaths were greater in DZ twins (58/520, 11.2%) than MZ twins (38/508, 7.5%). Ischemic heart disease concordances were 2.3 times higher in MZ pairs and 2.8 times higher in DZ pairs than expected based on the prevalence of ischemic heart disease in the cohort. Family history scores for heart disease, calculated 14-18 years earlier at entry to the study, were significantly higher in DZ pairs where one or both members later developed ischemic heart disease and in corcordant MZ pairs than in twin-pairs without any subsequent heart disease. Concordance rates were not significantly different between MZ and DZ pairs. The results agree with previous suggestions that selection at enlistment into the armed services over 40 years ago, as well as later volunteering for the NHLBI twin study, resulted in a decline in the number of concordant MZ pairs.

Cause of Death↗
PubMed1991

Influence of placentation on high density lipoproteins in adult males: the NHLBI twin study.

Dizygotic (DZ) World War II veteran twins who participated in the National Heart Lung and Blood Institute (NHLBI) Twin Study have been reported to have greater variance than monozygotic (MZ) twins for plasma high-density lipoprotein cholesterol (HDL-C), cholesterol in the low-density fraction of HDL (HDL2-C) and apolipoprotein A-I, a major protein component of HDL. It was hypothesized that a possible source of this difference in zygosity variance could be prenatal environmental influences related to placental type. Dermatoglyphics were used to provide a retrospective index of placental type in a subset of the NHLBI MZ twins aged 59-70. The MZ twins classified as dichorionic were found to have significantly greater within-pair variability than the monochorionic MZ twins for HDL-C, HDL2-C and Apo A-I. These findings indicate that intrauterine environmental influences on HDL are manifest later in life.

Aged↗
PubMed1991

Estimates of heritability of plasma homocyst(e)ine levels in aging adult male twins.

Plasma homocyst(e)ine level was determined for 96 identical (MZ) and 92 fraternal (DZ) adult male twins aged 59-69. There was no difference in mean between MZ (10.31 nmol/ml) and DZ (10.36 nmol/ml) twins. The intraclass correlation coefficient of the log-transformed homocyst(e)ine level in 43 complete MZ and 39 complete DZ pairs was 0.55 and 0.19, respectively. The MZ correlation was significantly (p less than 0.05) greater than the DZ correlation, suggesting that the level of plasma homocyst(e)ine is genetically influenced.

Aged↗
PubMed1991

Salt sensitivity and resistance of blood pressure. Age and race as factors in physiological responses.

To identify characteristics that may contribute to salt sensitivity, we conducted studies of normal subjects who are at risk for hypertension, namely blacks, subjects older than 40 years of age, and first-degree relatives of subjects with essential hypertension. We also formulated definitions for salt sensitivity and resistance with a short-term volume expansion and contraction protocol and additionally from data derived from studies of long-term reduced dietary salt intake. We examined the effects of augmented potassium and calcium intake and also those of sodium as the chloride or the bicarbonate salt. Finally, we sought genetic markers that are associated with salt sensitivity. We found that salt sensitivity is a function of age and is more common in blacks than whites. These groups also have relatively delayed acute salt excretion compared with controls. We were unable to identify effects of gender. Haptoglobin phenotypes (HP 1-1) may facilitate identification of salt-sensitive individuals. A high potassium intake may make individuals less salt sensitive. Sodium chloride and sodium bicarbonate differ in their effects on blood pressure. Sodium chloride augments urinary calcium excretion, but sodium bicarbonate does not. Differences between susceptible and nonsusceptible groups, together with improved knowledge of electrolyte interactions, may facilitate our understanding of salt-sensitive hypertension.

Aging↗
PubMed1990

Dietary protein and blood pressure in monozygotic twins.

Cross-sectional studies relating blood pressure to dietary intake have shown equivocal results, in part due to the inability to take into account the strong genetic component of blood pressure. Intervention studies, using the same subject as his own control, often encounter additional problems when subjects are asked to adhere to an alternate diet. The National Heart, Lung, and Blood Institute Twin Study of middle-aged men provided information concerning the possible relationship of food-frequency-estimated nutrient intake to blood pressure while controlling for genetic effects in a free-living group of subjects. Using differences in monozygotic twins, a direct association of dietary protein intake and diastolic blood pressure was identified and persisted after adjustment for known covariates of blood pressure. Adjusting for known covariates and holding total calories constant, a 9-g difference in daily protein intake was directly associated with a 1 mm Hg difference in diastolic blood pressure. For protein intake as a percentage of total calories, a 2.18% difference was directly associated with a 1 mm Hg difference in diastolic blood pressure. The co-twin-control method provides a powerful design to address the interrelationships between nutrients and blood pressure in an observational as well as an experimental setting.

Adult↗
PubMed1990

Bone mass and anthropometric measurements in adult females.

Bone mass and anthropometrics were measured in 342 adult female twins, aged 25-79 (mean = 44.1 years) for the purpose of: (1) identifying which anthropometric measurements were most strongly associated with bone mass at various skeletal sites, and (2) determining the accuracy of combinations of these measurements in the prediction of bone mass. Among the eight skinfolds measured, the subscapular site was more strongly correlated with all bone mass measurements than any other skinfold. Similarly, calf circumference (among four sites) and biacromial width (among five frame size measurements) provided the strongest correlations within these groups of anthropometrics with all bone sites. The somewhat surprising consistency of these results was then tested in multivariable models for the prediction of bone mass. For the entire study group, each of the anthropometric measurements (subscapular skinfold, calf circumference and biacromial width) were independent, significant predictors of bone mass, even when height, weight and age were included in the models. These data suggest that frame size, muscularity and adiposity have independent effects on the skeleton, and that single measurements of each of these anthropometric characteristics are associated with all skeletal sites.

Adipose Tissue↗
PubMed1990

Smoking and alcohol consumption in adult male twins: genetic heritability and shared environmental influences.

This paper examines the heritability of cigarette smoking and alcohol consumption in 360 adult, male twin pair participants (176 monozygotic and 184 dizygotic pairs) in the second exam of the National Heart, Lung, and Blood Institute's Twin Study. Heritability estimates for smoking and alcohol use were calculated both before and after adjustment for shared variance between these behaviors and other characteristics, including coffee consumption, contact between twins, and two psychological traits: anger and activity. The purpose of the analysis was to determine the impact of adjustment for covariates on heritability estimates of smoking and alcohol use. Before adjustment, heritability of both smoking and alcohol use was highly significant and accounted for 52% and 60% of the variance, respectively. After adjustment for covariates, the heritability of smoking remained at 52% while that for alcohol use decreased to 43%. The fact that these estimates remained significant after adjustment for covariates leads to increased confidence about the role of genetics in both smoking and alcohol consumption.

Aged↗
PubMed1989

Genetic and environmental approaches to the prevention of hypertension.

While the familial and genetic nature of hypertension has long been recognized, the mechanisms involved are not clear. Recent studies suggest that an environmental factor, increased dietary sodium intake, may be required for the expression of this genetically determined form of hypertension. The evidence for this conclusion is based on physiological studies of humoral factors, renal function and the blood pressure response to sodium and volume expansion and reduction in several carefully characterized human populations.

Humans↗
PubMed1988

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↗