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


CONCLUSIONS
These results suggest that INPPL1 variants may be involved in mechanisms causing hypertension in metabolic syndrome patients specifically.
Marçano
Ana Carolina Braga
AC
Burke
Beverley
B
Gungadoo
Johannie
J
Wallace
Chris
C
Kaisaki
Pamela J
PJ
Woon
Peng Y
PY
Farrall
Martin
M
Clayton
David
D
Brown
Morris
M
Dominiczak
Anna
A
Connell
John M
JM
Webster
John
J
Lathrop
Mark
M
Caulfield
Mark
M
Samani
Nilesh
N
Gauguier
Dominique
D
Munroe
Patricia B
PB
D000328:Adult; D015331:Cohort Studies; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications* / Q000453:epidemiology / Q000503:physiopathology; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion; D006113:United Kingdom / Q000453:epidemiology
D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases