Margaret Stebbing

Genetic linkage of β and γ subunits of epithelial sodium channel to systolic blood pressure

Summary Background Mutations in the genes on chromosome 16p12 that encode the β and γ subunits of the epithelial sodium channel ( SCNNIB and SCNNIG , respectively) have been linked with rare sodium-dependent forms of low and high blood pressure. Other DNA variants in or around these genes may contribute to variation in blood pressure and the risk of coronary heart disease and stroke. Methods We studied 286 white families from the general population in Victoria, Australia. Each family comprised both parents and two natural children. All participants were genotyped at chromosome 16p12 by use of four highly polymorphic microsatellite markers. Quantitative phenotype measurements were correlated with genotype in identity-by-descent sibling-pair linkage analyses. Findings We found significant linkage between systolic blood pressure and chromosome 16p12 after parametric analyses (p=0·0003) and non-parametric analyses (p=0·001). The mean difference in systolic blood pressure between siblings identical-by-descent at these loci was half as large (7·1 mm Hg) as the difference between siblings non-identical at these loci (14·0 mm Hg, p=0·001). No linkage between chromosome 16p12 and diastolic blood pressure or body-mass index was observed. Interpretation Chromosome 16p12 and the SCNNIB and SCNNIG genes are implicated in the physiological variation of systolic blood pressure. Our findings are important in explaining individual cardiovascular risk within the general population.

Association of the Human Y Chromosome With High Blood Pressure in the General Population

Genetic variation in the Y chromosome has significant effects on male blood pressure in experimental animals, but the effects in humans are unknown. We examined the relationship between blood pressure and a polymorphic Hin dIII restriction site in the nonrecombining region of the Y chromosome in 409 randomly selected men from the general population. Carefully standardized measures of systolic and diastolic blood pressures were made. The Hin dIII restriction site was significantly more common (43.2%) in men in the lowest decile of the diastolic blood pressure distribution than men in the highest decile (15.9%, P =0.007). No significant difference in genotype frequency was observed between the lowest and highest deciles for systolic pressure (32.4% versus 27.8%, P =0.66). In the entire group, men with the Hin dIII restriction site had significantly lower diastolic blood pressures (81.2 mm Hg, SD:8.3, versus 83.2 mm Hg, SD:8.7, P =0.03). No significant differences in systolic blood pressure (130.6 mm Hg, SD:14.7, versus 128.3 mm Hg, SD: 13.6) were observed in relation to genotypes. Our results indicate that genetic variation in the human Y chromosome is associated with high blood pressure and contributes significantly to the quantitative variation of male diastolic blood pressure in the general population.

Male pattern baldness is not associated with established cardiovascular risk factors in the general population

A number of studies have shown an association between male pattern baldness (MPB) and cardiovascular disease. Few of these studies, however, have examined whether MPB is a novel risk factor, or is associated with abnormalities of established coronary risk factors. We have therefore performed an analysis of MPB and cardiovascular risk factors in the general population. A total of 1219 male participants aged 18-70 years from the Victorian Family Heart Study were surveyed using a validated questionnaire for degree and pattern of baldness. Carefully standardized measures of height, weight, blood pressure, pulse rate, total and high-density lipoprotein cholesterol, and plasma fibrinogen were made. Subjects were grouped according to the degree and pattern of baldness as: no baldness, frontal baldness and vertex baldness. Bald men were older than non-bald men (P < 0.0001). Age was also associated with increased levels of coronary risk factors (P < 0.0001). When multiple regression was used to adjust for age differences, the levels of coronary risk factors were not significantly different between the bald and non-bald groups. The lack of association between baldness and established coronary risk factors implies that baldness may predispose to coronary heart disease through novel mechanisms yet to be defined.

Accuracy of national mortality codes in identifying adjudicated cardiovascular deaths.

Objective: This study investigated the sensitivity and specificity of the national mortality codes in identifying cardiovascular disease (CVD) deaths and documents methods of verification.

Linkage analysis of endothelial nitric oxide synthase gene with human blood pressure.

OBJECTIVE Endothelial nitric oxide exerts important effects on the regulation of vascular tone and structure. Variants of the endothelial nitric oxide synthase gene (eNOS) have been associated with hypertension and myocardial infarction, although some reports have shown negative linkage with hypertension. To examine whether the region encoding the eNOS gene is linked with physiological blood pressure variation, we undertook a linkage analysis of this region in the general population. DESIGN In healthy volunteer families, we used two independent quantitative linkage analyses to examine the relationship between genotypes and phenotypes, with both parametric and non-parametric and single-locus and multi-point methods. METHODS We selected 260 families comprising mother and father (aged 40-70 years) and two natural offspring (aged 18-30 years) from the Victorian Family Heart Study. After standardized measurement of clinical data and extraction of DNA, all family members were genotyped at five microsatellite loci including the CA repeat in the eNOS gene by a PCR method. The quantitative linkage analyses were conducted according to two different analysis programs, the Genetic Analysis System (GAS) and the MAPMAKER/SIBS. RESULTS With both linkage analyses, we found no linkage between any of the loci on chromosome 7q35-36 and the phenotypes systolic and diastolic blood pressure, mean arterial pressure, pulse pressure, pulse rate, weight, height and body mass index. CONCLUSION Based on these results, we conclude that in this population the eNOS gene is not linked to the physiological variation of blood pressure and other related phenotypes.

Sex, Genes And Blood Pressure

1. Throughout most of life, males have higher average blood pressures than females. This sexual dichotomy may be related to genetic factors including the X and Y sex chromosomes and genes that control sex steroids. Resultant physiological differences between men and women may also be relevant to the quantitative variation of blood pressure within the sexes.

Insulin gene polymorphism and premature male pattern baldness in the general population.

Insulin is found in hair follicles and may play a role in the regulation of androgen metabolism and the hair growth cycle, which are relevant to the loss of scalp hair known as male pattern baldness. An excess of dihydrotestosterone on balding scalp indicates that the condition is androgen dependent. Premature male pattern baldness may be the male phenotype of familial polycystic ovary syndrome, a condition characterized by high levels of androgens and insulin that has been linked to insulin gene polymorphism. Therefore, we studied possible associations between relevant insulin gene polymorphisms and premature male pattern baldness in the general community. We examined the distribution of three dimorphic restriction fragment length polymorphisms: HphI, PstI and FokI in cases consisting of 56 men aged 18-30 years with significant baldness, and in 107 control men aged 50 years or more with no indication of baldness. No significant differences between cases and controls in allele, genotype or haplotype frequencies were identified. We conclude that, in the general population, the insulin gene is not associated with premature male pattern baldness.

Linkage analysis of glucocorticoid and β2-adrenergic receptor genes with blood pressure and body mass index

Glucocorticoids and catecholamines exert important effects on cardiovascular physiology and metabolism. Variants of the glucocorticoid receptor gene (GRL) and the beta2-adrenergic receptor gene (ADRB2) have been associated with high blood pressure and obesity. These genes are close on human chromosome 5q31-5q32, and we undertook a linkage analysis of this region in 264 families from the general population in relation to systolic and diastolic blood pressure, body mass index, weight, height, and pulse rate. All family members were genotyped at four microsatellite loci (D5S207, D5S210, D5S519, and D5S119) located on chromosome 5q31-5q33.3. Using quantitative identity-by-descent sibling pair linkage analysis, we found that at no loci was genetic similarity associated with phenotypic similarity for systolic and diastolic blood pressure, body mass index, weight, height, or pulse rate. Although it is not possible to exclude the influence of specific combinations of certain GRL and ADRB2 polymorphisms, the absence of significant linkage in our population argues against a role for GRL or ADRB2 in physiological variation of blood pressure and body mass index.

Risk perception and risk communication: Is nanotechnology at the crossroads in Australia?

This presentation addresses the potential for nanotechnology development to be derailed, or at least delayed, by unresolved concerns about health and safety issues. Findings from surveys of risk perception indicate that availability of knowledge about health risks can both inform and fuel concerns. Trust in regulatory systems is one factor which can influence community perceptions of risk, and there remain some issues about whether the regulatory systems are fully capable of identifying and managing these risks.