Association of polymorphisms in GPR10, the gene encoding the prolactin-releasing peptide receptor with blood pressure, but not obesity, in a U.K. Caucasian population.
Prolactin-releasing peptide (PrRP) and its G-protein-coupled receptor, GPR10, have been implicated in the central control of appetite and blood pressure. To determine whether mutations in these genes might contribute to morbid obesity, we screened both genes in 94 subjects with severe early-onset obesity. Four rare silent variants in PrRP and eight polymorphisms in GPR10 were found, two of which (V283I and P305L) altered amino acid sequence but were also found in U.K. Caucasian control subjects. Cells expressing the P305L variant receptor generated less intracellular calcium in response to PrRP than cells expressing the wild-type receptor. To examine whether genetic variation of the GPR10 locus might be associated with phenotypes relevant to obesity and/or blood pressure, the most common noncoding (G-62A) and coding (C914T [P305L]) polymorphisms were typed in 1,084 U.K. Caucasians. While no association was found with BMI, carriers of the P305L allelic variant had significantly lower systolic (123.95 vs. 128.55 mmHg, P < 0.05) and diastolic (74.90 vs. 78.20 mmHg, P < 0.01) blood pressure than wild-type subjects. In conclusion, we have conducted the first genetic study of GPR10 and its ligand PrRP in relation to metabolic phenotypes and have identified an association between GPR10 polymorphisms and diastolic and systolic blood pressure. The alteration in signaling properties of the receptor produced by P305L may provide a functional basis for this association.
Bhattacharyya
Sumit
S
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, U.K.
Luan
Jian'an
J
Challis
Benjamin
B
Schmitz
Catherine
C
Clarkson
Paul
P
Franks
Paul W
PW
Middelberg
Rita
R
Keogh
Julia
J
Farooqi
I Sadaf
IS
Montague
Carl
C
Brennand
John
J
Wareham
Nicholas J
NJ
O'Rahilly
Stephen
S
D001794:Blood Pressure / Q000235:genetics*; D006801:Humans; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled; D006113:United Kingdom; D044465:White People / Q000235:genetics*
C112345:PRLHR protein, human; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled