Physiology - Research Publications

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Author: Harrap, Stephen × Start date: 2000 × End date: 2009 ×

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    Androgen Receptor Copy Number Variation and Androgenetic Alopecia: A Case-Control Study
    Cobb, JE ; White, SJ ; Harrap, SB ; Ellis, JA ; Fairhead, C (PUBLIC LIBRARY SCIENCE, 2009-04-02)
    BACKGROUND: The functional polymorphism that explains the established association of the androgen receptor (AR) with androgenetic alopecia (AGA) remains unidentified, but Copy Number Variation (CNV) might be relevant. CNV involves changes in copy number of large segments of DNA, leading to the altered dosage of gene regulators or genes themselves. Two recent reports indicate regions of CNV in and around AR, and these have not been studied in relation to AGA. The aim of this preliminary case-control study was to determine if AR CNV is associated with AGA, with the hypothesis that CNV is the functional AR variant contributing to this condition. METHODOLOGY/PRINCIPAL FINDINGS: Multiplex Ligation-dependent Probe Amplification was used to screen for CNV in five AR exons and a conserved, non-coding region upstream of AR in 85 men carefully selected as cases and controls for maximal phenotypic contrast. There was no evidence of CNV in AR in any of the cases or controls, and thus no evidence of significant association between AGA and AR CNV. CONCLUSIONS/SIGNIFICANCE: The results suggest this form of genomic variation at the AR locus is unlikely to predispose to AGA.
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    Combined effects of routine blood pressure lowering and intensive glucose control on macrovascular and microvascular outcomes in patients with type 2 diabetes: New results from the ADVANCE trial.
    Zoungas, S ; de Galan, BE ; Ninomiya, T ; Grobbee, D ; Hamet, P ; Heller, S ; MacMahon, S ; Marre, M ; Neal, B ; Patel, A ; Woodward, M ; Chalmers, J ; ADVANCE Collaborative Group, ; Cass, A ; Glasziou, P ; Harrap, S ; Lisheng, L ; Mancia, G ; Pillai, A ; Poulter, N ; Perkovic, V ; Travert, F (American Diabetes Association, 2009-11)
    OBJECTIVE: To assess the magnitude and independence of the effects of routine blood pressure lowering and intensive glucose control on clinical outcomes in patients with long-standing type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a multicenter, factorial randomized trial of perindopril-indapamide versus placebo (double-blind comparison) and intensive glucose control with a gliclazide MR-based regimen (target A1C 0.1): the separate effects of the two interventions for the renal outcomes and death appeared to be additive on the log scale. Compared with neither intervention, combination treatment reduced the risk of new or worsening nephropathy by 33% (95% CI 12-50%, P = 0.005), new onset of macroalbuminuria by 54% (35-68%, P < 0.0001), and new onset of microalbuminuria by 26% (17-34%). Combination treatment was associated with an 18% reduction in the risk of all-cause death (1-32%, P = 0.04). CONCLUSIONS: The effects of routine blood pressure lowering and intensive glucose control were independent of one another. When combined, they produced additional reductions in clinically relevant outcomes.