Citations

Background —Elevated blood pressure is a risk factor for cardiovascular, cerebrovascular, and renal diseases. Complex mechanisms of blood pressure regulation pose a challenge to identifying genetic factors that influence interindividual blood pressure variation in the population at large. Methods and Results —We performed a genome-wide linkage analysis of systolic blood pressure in humans using an efficient, highly discordant, full-sibling design. We identified 4 regions of the human genome that show statistical significant linkage to genes that influence interindividual systolic blood pressure variation (2p22.1 to 2p21, 5q33.3 to 5q34, 6q23.1 to 6q24.1, and 15q25.1 to 15q26.1). These regions contain a number of candidate genes that are involved in physiological mechanisms of blood pressure regulation. Conclusions —These results provide both novel information about genome regions in humans that influence interindividual blood pressure variation and a basis for identifying the contributing genes. Identification of the functional mutations in these genes may uncover novel mechanisms for blood pressure regulation and suggest new therapies and prevention strategies.

Background —After genome-wide linkage analyses of blood pressure levels, we resequenced 5 positional candidate genes in a linkage region on chromosome 5 and genotyped selected variants in several family samples from Rochester, Minn. Methods and Results —In a sample of 55 pedigrees containing ≥1 sibling-pair(s) discordant for systolic blood pressure, polymorphisms within the β 2 -adrenergic receptor gene (Arg16Gly, P =0.009) and the glutathione peroxidase 3 gene (−302G→A, P =0.037; −623A→C, P =0.013) were significantly related to blood pressure levels. In a second sample of 298 nuclear families (n=1283 individuals), the Arg16Gly polymorphism was significantly associated with diastolic blood pressure in family-based analyses ( P =0.016) and with both diastolic ( P =0.009) and mean arterial blood pressure ( P =0.038) in analyses of the parental generation only. Neither polymorphism in the glutathione peroxidase 3 gene was associated with blood pressure levels in this sample. An additional 291 families (n=1240 individuals) were added to the nuclear family sample, and the Gln27Glu polymorphism in the β 2 -adrenergic receptor gene was significantly associated with both systolic ( P =0.034) and mean arterial blood pressure ( P =0.035) in the parental generation of the combined 589 families. The frequencies of both the Gly16 and Glu27 alleles were higher in hypertensives than in normotensives (0.649 versus 0.604 and 0.490 versus 0.429, respectively), and the odds ratio for the occurrence of hypertension was 1.80 (95% confidence interval, 1.08 to 3.00; P =0.023) for the Glu27 allele. Conclusions —The results of this study provide support for further detailed investigations of the mechanistic pathways by which variations in the β 2 -adrenergic receptor gene may influence blood pressure levels.

Abstract Context: Surveillance of patients with differentiated thyroid cancer (DTC) is achieved using serum thyroglobulin (Tg), neck ultrasonography (US), and recombinant human TSH (rhTSH)-stimulated Tg (Tg-stim). Objective: Our primary aim was to assess the utility of rhTSH Tg-stim in patients with suppressed Tg (Tg-supp) below 0.1 ng/ml using a sensitive assay. Our secondary aims were to assess the utility of US and to summarize the profile of subsequent Tg-supp measures. Design: This is a retrospective study conducted at two sites of an academic institution. Patients: A total of 163 patients status after thyroidectomy and radioactive iodine treatment who had Tg-supp below 0.1 ng/ml and rhTSH Tg-stim within 60 d of each other were included. Results: After rhTSH stimulation, Tg remained below 0.1 ng/ml in 94 (58%) and increased to 0.1–0.5 in 56 (34%), more than 0.5–2.0 in nine (6%), and above 2.0 ng/ml in four (2%) patients. Serial Tg-supp levels were obtained in 138 patients followed over a median of 3.6 yr. Neck US were performed on 153 patients; suspicious exams had fine-needle aspiration (FNA). All positive FNA were identified around the time of the initial rhTSH test. Six of seven recurrences were detected by US (Tg-stim >2.0 ng/ml in one, 0.8 in one and ≤0.5 in four). One stage IV patient had undetectable Tg-stim. Conclusion: In patients with DTC whose T4-suppressed serum Tg is below 0.1 ng/ml, long-term monitoring with annual Tg-supp and periodic neck US are adequate to detect recurrences. In our experience, rhTSH testing does not change management and is not needed in this group of patients.

While anal sphincter neurogenic injury documented by needle electromyography (EMG) has been implicated to cause fecal incontinence (FI), most studies have been uncontrolled. Normal values and the effects of age on anal sphincter motor unit potentials (MUP) are ill defined. The functional significance of anal sphincter neurogenic injury in FI is unclear. Anal pressures and EMG were assessed in 20 asymptomatic nulliparous women (age, 38 ± 5 yr; mean ± SE) and 20 women with FI (54 ± 3 yr). A computerized program quantified MUP duration and phases. These parameters and MUP recruitment were also semiquantitatively assessed by experienced electromyographers in real time. Increasing age was associated with longer and more polyphasic MUP in nulliparous women by quantitative analysis. A higher proportion of FI patients had prolonged (1 control, 7 patients, P = 0.04) and polyphasic MUP (2 controls, 9 patients, P = 0.03) at rest but not during squeeze. Semiquantitative analyses identified neurogenic or muscle injury in the anal sphincter (11 patients) and other lumbosacral muscles (4 patients). There was substantial agreement between quantitative and semiquantitative analyses (κ statistic 0.63 ± 95% CI: 0.32–0.96). Anal resting and squeeze pressures were lower ( P ≤ 0.01) in FI than controls. Anal sphincter neurogenic or muscle injury assessed by needle EMG was associated ( P = 0.01) with weaker squeeze pressures (83 ± 10 mmHg vs. 154 ± 30 mmHg) and explained 19% ( P = 0.01) of the variation in squeeze pressure. Anal sphincter MUP are longer and more polyphasic in older than younger nulliparous women. Women with FI have more severe neurogenic or muscle anal sphincter injury, which is associated with lower squeeze pressures.