Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.

Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets

Reference values of serum IgA subclasses in Caucasian adults by immunonephelometry.

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Relationship between venous and arterial haemodynamics during postural changes in venous insufficiency

Objective: To study the changes in central haemodynamics and the relationship between arterial blood pressure and the venous dynamics of the lower limbs in patients with venous insufficiency. Design: Prospective haemodynamic study during postural changes in 14 patients with venous insufficiency with no other concomitant cardiovascular disease or disturbances in autonomic nervous system. Setting: Department of Cardiology and Angiology, University Hospital, Gent, Belgium. Patients: Fourteen patients with venous valve insufficiency in the lower limbs. Interventions: Measurements of arterial blood pressure, heart rate, stroke volume and cardiac output were performed in the supine position after 30 min rest and 5, 15 and 30 min after standing and during the recovery. Venous pressure at the ankle and calf circumference were also measured. Main outcome measures: Changes in cardiac output and total peripheral vascular resistance in order to maintain blood pressure during postural changes. Results: Arterial blood pressure was maintained constant owing to an increase in total peripheral vascular resistance despite a decrease in cardiac output. Venous pressure is also related to arterial blood pressure. Conclusions: The arterial and venous systems, even in venous insufficiency, are integrated to maintain blood pressure constant during postural changes