RGD Reference Report - Mutations in the glucokinase regulatory protein gene in 2p23 in obese French caucasians. - Rat Genome Database

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Mutations in the glucokinase regulatory protein gene in 2p23 in obese French caucasians.

Authors: Veiga-da-Cunha, M  Delplanque, J  Gillain, A  Bonthron, DT  Boutin, P  Van Schaftingen, E  Froguel, P 
Citation: Veiga-da-Cunha M, etal., Diabetologia. 2003 May;46(5):704-11. Epub 2003 May 9.
RGD ID: 1626607
Pubmed: PMID:12739015   (View Abstract at PubMed)
DOI: DOI:10.1007/s00125-003-1083-y   (Journal Full-text)

AIMS/HYPOTHESIS: Glucokinase regulatory protein (GKRP) controls the activity of glucokinase in liver but possibly also in some areas of the central nervous system, suggesting that it could play a role in body mass control. Its gene is located in a region (2p21-23) linked to serum leptin levels. Our goal was to investigate whether mutations in the GKRP gene were associated with obesity. METHODS: Mutations were sought in the GKRP gene of 57 patients from the families of the French genome-wide scan for obesity that contributed most to the positive LOD score with 2p21-23. The identified mutations were further sought in 720 unrelated obese individuals and 384 individuals of normal weight and their effect on the properties of recombinant GKRP were investigated. RESULTS: The most frequent mutation (Pro446Leu) had a similar allele frequency in the obese (0.63) and normal weight (0.64) subjects and did not affect the properties of GKRP. Similarly, no effect on the properties of GKRP was observed with Arg590Tyr, found in 10 out of 720 obese subjects and in 2 out of 384 control subjects (p=0.18). Mutation Arg227Stop was found in one obese family and in 1 out of 384 control subjects and led to an insoluble protein. Mutation Arg518Gln, replacing a conserved residue, led to a marked decrease in the affinity of GKRP for both fructose 6-phosphate and fructose 1-phosphate and to a destabilization of GKRP. However, this mutation did not co-segregate with obesity in the single family in which it was found. CONCLUSIONS/INTERPRETATION: Mutations that affect the properties of GKRP are found in the French population, but they do not seem to account for the linkage between the 2p23 locus and quantitative markers of obesity.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
obesity no_associationIAGP 1626607DNA:mutations:CDS:no association with mutations P446L more ...RGD 
obesity no_associationISOGCKR (Homo sapiens)1626607; 1626607 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gckr  (glucokinase regulator)

Genes (Mus musculus)
Gckr  (glucokinase regulatory protein)

Genes (Homo sapiens)
GCKR  (glucokinase regulator)


Additional Information