RGD Reference Report - Variants of GCKR affect both beta-cell and kidney function in patients with newly diagnosed type 2 diabetes: the Verona newly diagnosed type 2 diabetes study 2. - Rat Genome Database

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Variants of GCKR affect both beta-cell and kidney function in patients with newly diagnosed type 2 diabetes: the Verona newly diagnosed type 2 diabetes study 2.

Authors: Bonetti, S  Trombetta, M  Boselli, ML  Turrini, F  Malerba, G  Trabetti, E  Pignatti, PF  Bonora, E  Bonadonna, RC 
Citation: Bonetti S, etal., Diabetes Care. 2011 May;34(5):1205-10. doi: 10.2337/dc10-2218. Epub 2011 Mar 16.
RGD ID: 7242280
Pubmed: PMID:21411509   (View Abstract at PubMed)
PMCID: PMC3114499   (View Article at PubMed Central)
DOI: DOI:10.2337/dc10-2218   (Journal Full-text)

OBJECTIVE: In genome-wide association studies, performed mostly in nondiabetic individuals, genetic variability of glucokinase regulatory protein (GCKR) affects type 2 diabetes-related phenotypes, kidney function, and risk of chronic kidney disease (CKD). We tested whether GCKR variability affects type 2 diabetes or kidney-related phenotypes in newly diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS: In 509 GAD-negative patients with newly diagnosed type 2 diabetes, we 1) genotyped six single nucleotide polymorphisms in GCKR genomic region: rs6717980, rs1049817, rs6547626, rs780094, rs2384628, and rs8731; 2) assessed clinical phenotypes, insulin sensitivity by the euglycemic insulin clamp, and beta-cell function by state-of-the-art modeling of glucose/C-peptide curves during an oral glucose tolerance test; and 3) estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease formula. RESULTS: The major alleles of rs6717980 and rs2384628 were associated with reduced beta-cell function (P < 0.05), with mutual additive effects of each variant (P < 0.01). The minor alleles of rs1049817 and rs6547626 and the major allele of rs780094 were associated with reduced eGFR according to a recessive model (P < 0.03), but with no mutual additive effects of the variants. Additional associations were found between rs780094 and 2-h plasma glucose (P < 0.05) and rs8731 and insulin sensitivity (P < 0.05) and triglycerides (P < 0.05). CONCLUSIONS: Our findings are compatible with the idea that GCKR variability may play a pathogenetic role in both type 2 diabetes and CKD. Genotyping GCKR in patients with newly diagnosed type 2 diabetes might help in identifying patients at high risk for metabolic derangements or CKD.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
type 2 diabetes mellitus  IMP 7242280 RGD 
type 2 diabetes mellitus  ISOGCKR (Homo sapiens)7242280; 7242280 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gckr  (glucokinase regulator)

Genes (Mus musculus)
Gckr  (glucokinase regulatory protein)

Genes (Homo sapiens)
GCKR  (glucokinase regulator)


Additional Information