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

J Med Genet. 2007 Sep;44(9):603-5. doi: 10.1136/jmg.2007.049718. Epub 2007 Jun 8.

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.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Cohort Studies
  • Female
  • Haplotypes / genetics
  • Humans
  • Hypertension / etiology
  • Hypertension / genetics*
  • Insulin Resistance / genetics
  • Linkage Disequilibrium
  • Male
  • Metabolic Syndrome / complications*
  • Metabolic Syndrome / epidemiology
  • Metabolic Syndrome / physiopathology
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
  • Phosphoric Monoester Hydrolases / genetics*
  • Polymorphism, Single Nucleotide*
  • Sequence Deletion
  • United Kingdom / epidemiology

Substances

  • Phosphoric Monoester Hydrolases
  • INPPL1 protein, human
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases