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  • Genetic association analysis of inositol polyphosphate phosphatase-like 1 (INPPL1, SHIP2) variants with essential hypertension

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Genetic association analysis of inositol polyphosphate phosphatase-like 1 (INPPL1, SHIP2) variants with essential hypertension
  1. Ana Carolina Braga Marçano1,
  2. Beverley Burke1,
  3. Johannie Gungadoo1,
  4. Chris Wallace1,
  5. Pamela J Kaisaki2,
  6. Peng Y Woon2,
  7. Martin Farrall3,
  8. David Clayton4,
  9. Morris Brown4,
  10. Anna Dominiczak5,
  11. John M Connell5,
  12. John Webster6,
  13. Mark Lathrop7,
  14. Mark Caulfield1,
  15. Nilesh Samani8,
  16. Dominique Gauguier2,
  17. Patricia B Munroe1
  1. 1Clinical Pharmacology and The Genome Centre, Barts and The London School of Medicine and Dentistry, London, UK
  2. 2The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
  3. 3Department of Cardiovascular Medicine, University of Oxford, Wellcome Trust Centre for Human Genetics, Oxford, UK
  4. 4Clinical Pharmacology and the Cambridge Institute of Medical Research, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK
  5. 5BHF Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, University of Glasgow, Western Infirmary, Glasgow, UK
  6. 6Medicine and Therapeutics, Aberdeen Royal Infirmary, Aberdeen, UK
  7. 7Centre National de Genotypage, Evry, France
  8. 8Cardiology, University of Leicester, Glenfield Hospital, Leicester, UK
  1. Correspondence to:
 Patricia B Munroe
 PhD, Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ; p.b.munroe{at}qmul.ac.uk

Abstract

Background: Inositol polyphosphate phosphatase-like 1 (INPPL1, SHIP2) is a negative regulator of insulin signalling and has previously been found to be associated with hypertension, obesity and type 2 diabetes in a cohort of families with diabetes in the UK presenting features of 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.

Objective and methods: 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 families with severe hypertension from the BRIGHT study transmission disequilibrium test cohort.

Results: We found no evidence of significant association between hypertension and any of the three INPPL1 polymorphisms or haplotypes (p>0.1).

Conclusion: These results suggest that INPPL1 variants may be involved in mechanisms causing hypertension in metabolic syndrome patients specifically.

  • BRIGHT, British Genetics of Hypertension
  • CEPH, Centre d’Etudes du Polymorphisme Humain
  • DIF, Diabetes in Families
  • EH, essential hypertension
  • GK, Goto–Kakizaki
  • HWE, Hardy–Weinberg equilibrium
  • SHR, spontaneously hypertensive rat
  • SNP, single nucleotide polymorphism
  • TDT, transmission disequilibrium test
  • hypertension
  • diabetes
  • association
  • INPPL1

https://doi.org/10.1136/jmg.2007.049718

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    Footnotes

    • Competing interests: None declared.

    • Published Online First 8 June 2007