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Genetic association analysis of inositol polyphosphate phosphatase-like 1 (INPPL1, SHIP2) variants with essential hypertension
  1. Ana Carolina Braga Marcano (a.c.bragamarcano{at}qmul.ac.uk)
  1. Bart't and The London School of Medicine and Dentistry, United Kingdom
    1. Beverley Burke (bburke{at}sgul.ac.uk)
    1. Bart't and The London School of Medicine and Dentistry, United Kingdom
      1. Johannie Gungadoo (johannie{at}gungadoo.com)
      1. Bart't and The London School of Medicine and Dentistry, United Kingdom
        1. Chris Wallace (c.wallace{at}qmul.ac.uk)
        1. Bart't and The London School of Medicine and Dentistry, United Kingdom
          1. Pamela J Kaisaki
          1. University of Oxford, United Kingdom
            1. Peng Y Woon
            1. University of Oxford, United Kingdom
              1. Martin Farrall
              1. University of Oxford, United Kingdom
                1. David Clayton
                1. University of Cambridge, Addenbrooke's Hospital, United Kingdom
                  1. Morris Brown
                  1. University of Cambridge, Addenbrooke's Hospital, United Kingdom
                    1. Anna Dominiczak
                    1. University of Glasgow, United Kingdom
                      1. John M Connell
                      1. University of Glasgow, United Kingdom
                        1. John Webster
                        1. Aberdeen Royal Infirmary, United Kingdom
                          1. Mark Lathrop
                          1. Centre National de Genotypage, France
                            1. Mark Caulfield
                            1. Bart's and The London School of Medicine and Dentistry, United Kingdom
                              1. Nilesh Samani
                              1. University of Leicester, United Kingdom
                                1. Dominique Gauguier
                                1. University of Oxford, United Kingdom
                                  1. Patricia B Munroe (p.b.munroe{at}qmul.ac.uk)
                                  1. Bat's and the London School of Medicine and Dentistry, United Kingdom

                                    Abstract

                                    Inositol polyphosphate phosphatase-like 1 (INPPL1, SHIP2) is a negative regulator of insulin signalling and was previously found to be associated with hypertension, obesity and type 2 diabetes in a cohort of British diabetic families presenting features of the metabolic syndrome. In particular, a haplotype of three genetic polymorphisms (rs2276047, rs9886 and an insertion/deletion polymorphism in intron 1) was found to be strongly associated with increased susceptibility to hypertension. To assess if INPPL1 variants play a direct role in the development of essential hypertension, we genotyped the three previously associated INPPL1 polymorphisms in a cohort of 712 severely hypertensive TDT families from the BRIGHT study. We found no evidence of significant association between hypertension and any of the three INPPL1 polymorphisms or haplotypes (p > 0.1). These results suggest that INPPL1 variants may be involved in mechanisms causing hypertension specifically in the context of the metabolic syndrome.

                                    • Association study
                                    • Diabetes
                                    • Hypertension
                                    • INPPL1

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