Gender-specific determinants of goiter

Despite the strong implications of differences between females and males in the risk of goiter, gender-specific issues have not been extensively addressed in investigations of goiter prevalence. The objective of our analysis was to investigate the gender-specific determinants of goiter. Between April 2001 and April 2002. A total of 853 healthy employees from 4 institutions in the western part of Germany between 18 and 68 yr of age were examined by ultrasound of the neck to determine the thyroid volume. Information on sex, age, daily use of iodized salt, the history of goiter in the first-degree relatives, type and amount of smoking, oral contraceptives, and number of pregnancies were assessed by standardized questionnaires. Gender-specific predictors of goiter prevalence were assessed by multivariate logistic regression. The overall prevalence of goiter among study subjects was 204/853 (23.9%). Goiter was present in 80 out of 370 females (21.6%) vs 124/483 (25.7%) in males. In general, smoking (p<0.0001), increasing age (p<0.0001), and lack of daily intake of iodized salt (p=0.004) were associated with goiter prevalence, but not sex (p=0.39) and family history of goiter (p=0.16). In 370 females, parity (p=0.004) and lack of daily intake of iodized salt (p=0.01) were the major determinants for goiter, whereas age (p=0.18), oral contraceptives (p=0.82), family history of goiter (p=0.33), and smoking (p=0.09) did not affect goiter prevalence. In 483 males, smoking (p<0.0001) and age (p<0.001) affected goiter prevalence, but not family history of goiter (p=0.39), and the iodine status failed just to reach the significant level (p=0.08) in this analysis. Gender-specific determinants of goiter are parity and iodine status in females and smoking and increasing age in males.     

Common genetic determinants of intraocular pressure and primary open-angle glaucoma

Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p = 1.4×10⁻⁸), and with rs7555523, located in TMCO1 at 1q24.1 (p = 1.6×10⁻⁸). In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p = 2.4×10⁻² for rs11656696 and p = 9.1×10⁻⁴ for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.     

Familial determinants of blood pressure in Northeastern Brazil

Summary Genetic heritability in this triracial population is 0.41 for systolic pressure in children, 0.14 for systolic pressure in adults, and 0.34 for diastolic pressure in both generations. Cultural inheritance is much smaller, and there is no evidence of maternal effects or major loci.     

Multivariate models for human genetic analysis: aggregation, coaggregation, and tracking of systolic blood pressure and weight.

A multivariate path model parameterizing the sources of familial aggregation and coaggregation of systolic blood pressure and weight, as well as their tracking across time, is applied to longitudinal data collected in Muscatine, Iowa. Genetic, common household, and individual environmental effects, pleiotropy, and a direct regression effect of blood pressure on weight are parameterized. The sample consisted of 998 individuals distributed in 261 families of whom 601 were measured on four successive occasions. The data were divided with times 1 and 2 forming group 1, and times 3 and 4, group 2. Model fitting and estimation was performed using group 1, followed by testing the model and estimates using the data in group 2. Heritability estimates for systolic blood pressure and weight were .15 and .54, respectively. The genetic correlation between these traits was nonsignificant, but there was a significant direct regression effect. The results indicate that 30% of the full-sib correlation for systolic blood pressure is attributable to the aggregation of weight. In terms of tracking, 59% and 60% of the predicted systolic blood pressure and weight correlations, respectively, were attributable to genetic effects. Testing the model from group 1 in group 2 indicates that the qualitative relationships between blood pressure and weight are stable with time.     

Lymphoid organ weights and organ:body weight ratios of growing beagles

Although dogs, especially beagles, are used extensively in biological and clinical investigations, the literature dealing with normal biological measurements of their lymphoid organs is scanty. This study was undertaken to provide the information on the weight of lymphoid organs of beagles. The thymus, spleen, and prescapular, popliteal, and mesenteric lymph nodes of 95 normal beagle dogs, from one day to 11 months of age, were weighed and compared with body weights. The weight of the thymus and spleen increased drastically at and after 2 months of age, although the organ:body weight ratios remained the same at 2 months of age and decreased afterward. Similar increases in the weight of the mesenteric lymph node complex, but with an increase in the organ:body weight ratio, occurred also at and after 2 months of age, reflecting the importance of the gut-associated lymphoid organs after weaning. The increases in the size of the cutaneous nodes, prescapular and popliteal, were less pronounced and their organ:body weight ratios remained the same from birth through 11 months of age.     

Genome-informed approach to identify genetic determinants of Flavobacterium psychrophilum phage susceptibility

The fish pathogen Flavobacterium psychrophilum infects farmed salmonids worldwide, and application of bacteriophages has been suggested for controlling disease outbreaks in aquaculture. Successful application of phages requires detailed knowledge about the variability in phage susceptibility of the host communities. In this study, we analysed the genetic diversity of F. psychrophilum hosts and phages from the Baltic Sea area to identify genetic determinants of phage-host interaction patterns. A host range analysis of 103 phages tested against 177 F. psychrophilum strains (18 231 phage–host interactions) identified nine phage clusters, infecting from 10% to 91% of the strain collection. The core genome-based comparison of 35 F. psychrophilum isolates revealed an extremely low overall genomic diversity (>99.5% similarity). However, a small subset of 16 ORFs, including genes involved in the type IX secretion system (T9SS), gliding motility and hypothetical cell-surface related proteins, exhibited a highly elevated genetic diversity. These specific genetic variations were linked to variability in phage infection patterns obtained from experimental studies, indicating that these genes are key determinants of phage susceptibility. These findings provide novel insights on the molecular mechanisms determining phage susceptibility in F. psychrophilum and emphasizes the importance of phages as drivers of core genomic diversity in this pathogen.     

Dietary sodium and arterial blood pressure: evidence against genetic susceptibility.

Thirty five subjects with both parents in the top third of their age specific blood pressure distributions and 31 subjects with both parents in the bottom third of their blood pressure distributions restricted their intake of sodium for eight weeks while taking part in a double blind, randomised crossover trial of supplements of sodium and placebo. A comparison of two periods of four weeks at different intakes of sodium showed no differences in blood pressure in either the groups as a whole or the subgroups who complied best with the diet and tablets. In the compliant subgroups mean urinary sodium excretions were above 120 mmol(mEq) and below 50 mmol/day. The study provides evidence against the hypothesis that people with a family history of high blood pressure are more susceptible in their blood pressure response to dietary sodium.     

Relation between birth weight and blood pressure: longitudinal study of infants and children.

OBJECTIVE--To study the relation between birth weight and systolic blood pressure in infancy and early childhood. DESIGN--Longitudinal study of infants from birth to 4 years of age. SETTING--A middle class community in the Netherlands. PARTICIPANTS--476 Dutch infants born in 1980 to healthy women after uncomplicated pregnancies. MAIN OUTCOME MEASURES--Systolic blood pressure and body weight measured at birth and at 3 months and 4 years of age; the relation between systolic blood pressure and birth weight as estimated by multiple regression models that include current weight and previous blood pressure and control for gestational age, length at birth, and sex. RESULTS--Complete data were available on 392 infants. At 4 years of age the relation between blood pressure and birth weight appeared to be U shaped; low and high birthweight infants had raised blood pressure. Current weight and previous blood pressure were also positively associated with blood pressure at that age. Low birthweight infants (birth weight < 3100 g) had a greater gain in blood pressure and weight in early infancy. High birthweight infants (birth weight > or = 3700 g) had high blood pressure at birth, and weight and blood pressure tended to remain high thereafter. CONCLUSIONS--Even among normal infants there seem to be subgroups defined by birth weight in which blood pressure is regulated differently. Future investigations are needed to examine the physiological basis of these differences. Studies of correlates of adult disease related to birth weight should investigate mechanisms related to increased risk separately in infants of low and high birth weight.     

Muscle strength and body composition as determinants of blood pressure in young men

The correlations of blood pressure to various indices of muscularity and fatness were studied in 183 young healthy men (mean age 19.7, SD 2.1 years). Systolic pressure showed significant positive correlations with body fat percentage, isometric strength of trunk extensors, body mass index, lean body mass, strength of leg extensors, heart rate, and the sum of four skinfolds. Diastolic pressure had significant positive correlations with body mass index, lean body mass, body fat percentage, sum of skinfolds, strength of leg extensors, strength of trunk extensors, and age. A stepwise selective multiple regression analysis for systolic pressure resulted in four significantly correlating variables: body fat percentage (p less than 0.001), heart rate (p less than 0.01), lean body mass (p less than 0.05), and strength of trunk extensors per kg body weight (p less than 0.05). For diastolic pressure the analysis resulted in two explaining variables: body mass index (p less than 0.001) and age (p less than 0.05). In a regression equation with 13 variables the strength of trunk flexors was negatively correlated with diastolic pressure. It is concluded that both fatness and muscularity are factors related to blood pressure in young men. The muscularity effect is more clearly associated with trunk and leg extensor strength.     

Gender-specific regional changes in genetic structure of muscularity in early adolescence

Loos, R., M. Thomis, H. H. Maes, G. Beunen, A. L. Claessens,C. Derom, E. Legius, R. Derom, and R. Vlietinck. Gender-specific regional changes in genetic structure of muscularity in early adolescence. J. Appl. Physiol. 82(6):1802-1810, 1997.Genetic and environmental influences on musclecircumference measurements of the extremities were estimated in 105 pairs of twins between 10 and 14 yr of age. Four circumferences,extended upper arm (EAC), forearm (FC), thigh (TC), and calf (CC), weremeasured. Univariate model fitting revealed that the largest part(87-95%) of the variance for all circumferences at most ages wasexplained by additive genetic factors. Sex differences were observedfor some age categories. Multivariate analyses showed a differentpattern evolving according to age and gender. In boys from 10 to 12 yrof age, one general genetic factor influenced all four circumferences.With increasing age, an arm-leg model emerged, one genetic factorinfluencing the arm and another genetic factor the leg circumferences.In young girls one genetic factor loaded on the proximal (EAC,TC) andanother on the distal (FC,CC) circumferences. With subjects at age 14 yr, an arm-leg model was observed. High genetic correlations indicatedthat genetic factors related to EAC, FC, TC, and CC did not actindependently. The age- and gender-specific changes in the geneticstructure suggest pubertal influences. This study shows that musclecircumferences are highly heritable characteristics and are therefore apromising starting point at which to locate their genes. Gene mappingcould validate the gender-specific change of the genetic structure withage and region.

     

Autonomic control of blood pressure in mice: basic physiology and effects of genetic modification

Control of blood pressure and of blood flow is essential for maintenance of homeostasis. The hemodynamic state is adjusted by intrinsic, neural, and hormonal mechanisms to optimize adaptation to internal and environmental challenges. In the last decade, many studies showed that modification of the mouse genome may alter the capacity of cardiovascular control systems to respond to homeostatic challenges or even bring about a permanent pathophysiological state. This review discusses the progress that has been made in understanding of autonomic cardiovascular control mechanisms from studies in genetically modified mice. First, from a physiological perspective, we describe how basic hemodynamic function can be measured in conscious conditions in mice. Second, we focus on the integrative role of autonomic nerves in control of blood pressure in the mouse, and finally, we depict the opportunities and insights provided by genetic modification in this area.     

Fenofibrate lowers blood pressure in two genetic models of hypertension

Fenofibrate, a commonly used lipid lowering drug, induces the expression of the gene coding for cytochrome P450-4A, whose major product is 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE, a potassium channel antagonist, could increase or decrease blood pressure (BP). We studied the effects of four weeks of oral fenofibrate on BP, urine output (UVol), plasma renin activity (PRA), and urine protein excretion in young (4-5 weeks) stroke prone spontaneously hypertensive rats (SHRSP), older (25 weeks) SHRSP, Dahl salt sensitive rats (Dahl S) on a high salt diet, Dahl S rats on a normal salt diet, and normotensive Sprague-Dawley (SD) rats. Fenofibrate prevented the increase in BP in 4-5 week old SHRSP, reduced BP in 25 week old SHRSP, but had no effect on BP in normotensive SD rats. Similarly, fenofibrate prevented the increase in BP in Dahl S rats on a high salt diet, but had no effect in Dahl S rats on a low salt diet. Fenofibrate increased UVol (and reduced weight gain) in young SHRSP and tended to increase it in other groups. It also increased PRA 2 to 5-fold in all groups except older SHRSP. Young SHRSP receiving fenofibrate excreted significantly less urine protein than control rats. The drug reduced proteinuria in Dahl S rats on high salt diet, but had no significant effect on proteinuria in other groups. In summary, fenofibrate reduced blood pressure and weight gain, increased UVol and PRA, and reduced urine protein excretion in young SHRSP. Other groups of animals showed these changes to a variable, but directionally similar extent. These findings are consistent with a natriuretic effect of fenofibrate.     

Factors affecting blood pressure during heavy weight lifting and static contractions.

Brachial arterial pressure was directly recorded in 31 healthy male volunteers through protocols examining the effects of the Valsalva maneuver, muscle size and strength, contraction force, contraction type (concentric, isometric, eccentric), changes in joint angle, and muscle fatigue on the blood pressure response to resistance exercise. Weight lifting at the same relative intensity produced similar increases in blood pressure, regardless of individual differences in muscle size or strength. Concentric, isometric, or eccentric exercise at the same relative intensity caused similar increases despite differences in force production. In weight lifting, the greatest increase in blood pressure occurred at the joint angle corresponding to the weakest point in the strength curve and the least at the angle corresponding to the strongest point. Isometric contractions of the same relative intensity at different joint angles produced identical blood pressures despite differences in absolute force production. When subjects attempted to maintain a maximum isometric contraction for 45 s, the blood pressure increase remained the same despite a marked diminution in force. Thus the magnitude of the blood pressure response depends on the degree of effort or central command and not actual force production. A brief Valsalva maneuver, which exaggerates the increase in blood pressure, is unavoidable when desired force production exceeds approximately 80% maximum voluntary contraction.     

Changes in blood pressure, body weight and urinary catecholamines during austerities

More than one hundred monks belonging to Nichirenshu, a major Buddhist sect in Japan, participated in the annual hundred days austerities during the winter. Cold water bathing, insufficient sleep, hunger and emotional impact are considered to be the major stressors experienced by the monks subjected to these austere regimes. This study was conducted to evaluate the endocrinological and physiological changes in twenty newcomer monks during the first four weeks of the austerities. The urinary concentration of noradrenaline (NOR) increased significantly during the first four weeks but not that of adrenaline (ADR). The changes in urinary concentration of ADR and NOR indicated the main stressors possibly to be low ambient temperature and hunger. NOR is thus probably a better indicator than ADR for evaluating stress under austere conditions. Blood pressure (BP) did not rise but the concentration of NOR was noted to increase. NOR may possibly be excreted in excessive amounts to maintain normal BP against hypotensive factors such as loss of body weight due to low calorie intake.     

Alcohol intake and blood pressure: a systematic review implementing a Mendelian randomization approach

Background

Alcohol has been reported to be a common and modifiable risk factor for hypertension. However, observational studies are subject to confounding by other behavioural and sociodemographic factors, while clinical trials are difficult to implement and have limited follow-up time. Mendelian randomization can provide robust evidence on the nature of this association by use of a common polymorphism in aldehyde dehydrogenase 2 (ALDH2) as a surrogate for measuring alcohol consumption. ALDH2 encodes a major enzyme involved in alcohol metabolism. Individuals homozygous for the null variant (*2*2) experience adverse symptoms when drinking alcohol and consequently drink considerably less alcohol than wild-type homozygotes (*1*1) or heterozygotes. We hypothesise that this polymorphism may influence the risk of hypertension by affecting alcohol drinking behaviour.

Methods and Findings

We carried out fixed effect meta-analyses of the ALDH2 genotype with blood pressure (five studies, n = 7,658) and hypertension (three studies, n = 4,219) using studies identified via systematic review. In males, we obtained an overall odds ratio of 2.42 (95% confidence interval [CI] 1.66–3.55, p = 4.8 × 10⁻⁶) for hypertension comparing *1*1 with *2*2 homozygotes and an odds ratio of 1.72 (95% CI 1.17–2.52, p = 0.006) comparing heterozygotes (surrogate for moderate drinkers) with *2*2 homozygotes. Systolic blood pressure was 7.44 mmHg (95% CI 5.39–9.49, p = 1.1 × 10⁻¹²) greater among *1*1 than among *2*2 homozygotes, and 4.24 mmHg (95% CI 2.18–6.31, p = 0.00005) greater among heterozygotes than among *2*2 homozygotes.

Conclusions

These findings support the hypothesis that alcohol intake has a marked effect on blood pressure and the risk of hypertension.