Associations Between 25-Hydroxyvitamin D and Total and γ' Fibrinogen and Plasma Clot Properties and Gene Interactions in a Group of Healthy Black South African Women.

The role of 25-hydroxyvitamin D [25(OH)D] in reducing the risk of cardiovascular disease (CVD) has been recognized, but the mechanisms involved are unclear. Researchers have discovered a link between vitamin D and fibrinogen. Until now, data on the relationship between vitamin D and the γ' splice variant of fibrinogen and fibrin clot characteristics remain unexplored. In this study, 25(OH)D, total and γ' fibrinogen, as well as turbidimetrically determined plasma clot properties, were quantified, and fibrinogen and FXIII SNPs were genotyped in 660 Black, apparently healthy South African women. Alarmingly, 16 and 45% of the women presented with deficient and insufficient 25(OH)D, respectively. Total fibrinogen and maximum absorbance (as a measure of clot density) correlated inversely, whereas γ' fibrinogen correlated positively with 25(OH)D. γ' fibrinogen increased whereas maximum absorbance decreased over the deficient, insufficient, and sufficient 25(OH)D categories before and after adjustment for confounders. 25(OH)D modulated the association of the SNPs regarding fibrinogen concentration and clot structure/properties, but did not stand after correction for false discovery rate. Because only weak relationships were detected, the clinical significance of the findings are questionable and remain to be determined. However, we recommend vitamin D fortification and supplementation to reduce the high prevalence of this micronutrient deficiency and possibly to improve fibrinogen and plasma clot structure if the relationships are indeed clinically significant. There is a need for large cohort studies to demonstrate the relationship between vitamin D and cardiovascular and inflammatory risk factors as well as to uncover the molecular mechanisms responsible.

Certain Associations Between Iron Biomarkers and Total and γ' Fibrinogen and Plasma Clot Properties Are Mediated by Fibrinogen Genotypes.

Introduction: Evidence for the relationship between body iron and cardiovascular disease (CVD) is inconsistent and mechanisms involved remain poorly understood. Therefore, we first investigated whether there are linear or non-linear relationships between iron status and total and γ' fibrinogen as well as plasma fibrin clot properties and, second, determined whether there are interactions with iron biomarkers and fibrinogen and FXIII single nucleotide polymorphisms (SNPs) in relation to fibrinogen concentration and functionality. Methods: In this cross-sectional analysis of 2,010 apparently healthy Black South Africans we quantified total and γ' fibrinogen, serum iron, ferritin and transferrin using standardized methods and calculated transferrin saturation (TS). Clot architecture and lysis were explored with a global analytical turbidity assay. The SNPs were determined through an Illumina BeadXpress® platform. Results: Total, but not %γ', fibrinogen negatively correlated with serum iron concentrations, although both decreased over iron tertiles. %γ' fibrinogen correlated negatively with transferrin and decreased over the transferrin tertiles. A weak negative association between total fibrinogen and TS was detected with fibrinogen decreasing over the TS tertiles and categories based on TS. Lag time correlated positively with transferrin and increased over transferrin tertiles, when adjusting for fibrinogen. Before adjusting for fibrinogen, lag time was shorter in those with adequate iron status based on TS than other iron subcategories. Clot lysis time (CLT) negatively correlated with ferritin and was longer in the first than in the third ferritin tertile. Among iron status categories based on ferritin, only CLT differed and was longer in those with adequate iron than with iron-overload. CLT negatively correlated with TS, albeit weakly, shortened over the TS tertiles and was shorter in those with adequate iron based on TS categories. Interactions were observed between FGB SNPs and some of the markers of iron status investigated, in relation to the clot properties with the most prominent associations detected in homozygous carriers of the variant alleles for whom increased iron status was more beneficial than for those harboring the wild-type alleles. Iron modulated the influence of the SNPs so that for the majority iron was beneficial in respect of clot properties, but even more so for a minority group harboring specific variant alleles. Conclusion: This is the first large-scale epidemiological study to relate fibrinogen concentration and functionality to markers of iron status and to take genetic factors into consideration. We have detected a relationship between iron biomarkers and fibrinogen as well as clot characteristics that are influenced by the genetic make-up of an individual.

An inverse association between calcium and adiposity in women with high fat and calcium intakes.

OBJECTIVES: To assess the association between calcium intake and body composition in African Black and White women. DESIGN: Cross-sectional survey. SETTING: Metabolic unit. PARTICIPANTS: A convenience sample of 106 White and 102 Black healthy urban women, 20-50 years old, stratified for body mass index (BMI). MAIN OUTCOME MEASURES: Dietary calcium intake, fat intake, BMI, percentage body fat, fasting plasma glucose and insulin, homeostasis model assessment of insulin resistance (HOMA-IR), oral glucose tolerance test (OGTT), blood pressure. METHODS: After an overnight fast, weight, height and blood pressure were measured, subjects underwent a 75-g OGTT, and blood samples were taken. Food frequency questionnaires were completed, and body composition was measured by anthropometry and air displacement plethysmography. RESULTS: Mean calcium and fat intakes were significantly higher in White women (1053.8 mg/day and 103.1 g/day, respectively) than in the Black women (523 mg/day and 69.2 g/day), resulting in higher calcium:fat-intake ratio in White women. After adjustment for age and total energy intake, significant negative correlations were found between calcium intake and fasting insulin (r = -.337, P = .01) and HOMA-IR (r = -.334, P = .01) in the White subjects. The calcium:fat ratio correlated negatively with BMI (r = -.328, P < .012), percentage body fat (r = -.336, P = .01), fasting insulin (r = -.374, P = .004), postprandial insulin (r = -.328, P = .01), and HOMA-IR (r = -.365, P = .005). In the Black subjects, a significant negative correlation was found between calcium intake and blood pressure. CONCLUSION: The association between calcium intake and percentage body fat, BMI, fasting glucose, and insulin were significant only with high intake of fat and calcium, which is not characteristic of the habitual diet of African women.