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

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.