RGD Reference Report - Association of GCKR rs780094, alone or in combination with GCK rs1799884, with type 2 diabetes and related traits in a Han Chinese population. - Rat Genome Database

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Association of GCKR rs780094, alone or in combination with GCK rs1799884, with type 2 diabetes and related traits in a Han Chinese population.

Authors: Qi, Q  Wu, Y  Li, H  Loos, RJ  Hu, FB  Sun, L  Lu, L  Pan, A  Liu, C  Wu, H  Chen, L  Yu, Z  Lin, X 
Citation: Qi Q, etal., Diabetologia. 2009 May;52(5):834-43. Epub 2009 Feb 25.
RGD ID: 2315983
Pubmed: PMID:19241058   (View Abstract at PubMed)
DOI: DOI:10.1007/s00125-009-1290-2   (Journal Full-text)

AIMS/HYPOTHESIS: The GCKR rs780094 and GCK rs1799884 polymorphisms have been reported to be associated with dyslipidaemia and type 2 diabetes in white Europeans. The aim of this study was to replicate these associations in Han Chinese individuals and to identify the potential mechanisms underlying these associations. METHODS: The single nucleotide polymorphisms rs780094 and rs1799884 were genotyped in a population-based sample of Han Chinese individuals (n = 3,210) and tested for association with risk of type 2 diabetes and related phenotypes. RESULTS: The GCKR rs780094 A allele was marginally associated with reduced risk of type 2 diabetes (OR 0.85, 95% CI 0.73-1.00, p value under an additive model [p((add))] = 0.05) and significantly associated with reduced risk of impaired fasting glucose (IFG) or type 2 diabetes (OR 0.86, 95% CI 0.77-0.96, p([add]) = 0.0032). It was also significantly associated with decreased fasting glucose and increased HOMA of beta cell function (HOMA-B) and fasting triacylglycerol levels (p([add]) = 0.0169-5.3 x 10(-6)), but not with HOMA of insulin sensitivity (HOMA-S). The associations with type 2 diabetes and IFG remained significant after adjustment for BMI, while adjustment for HOMA-B abolished the associations. The GCKR rs780094 was also associated with obesity and BMI, independently of its association with type 2 diabetes. The GCK rs1799884 A allele was significantly associated with decreased HOMA-B (p([add]) = 0.0005), but not with type 2 diabetes or IFG. Individuals with increasing numbers of risk alleles for both variants had significantly lower HOMA-B (p([add]) = 5.8 x 10(-5)) in the combined analysis. CONCLUSIONS/INTERPRETATION: Consistent with observations in white Europeans, the GCKR rs780094 polymorphism contributes to the risk of type 2 diabetes and dyslipidaemia in Han Chinese individuals. In addition, we showed that the effect on type 2 diabetes is probably mediated through impaired beta cell function rather than through obesity.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
type 2 diabetes mellitus  IAGP 2315983DNA:polymorphism: :rs780094 (human)RGD 
type 2 diabetes mellitus  ISOGCKR (Homo sapiens)2315983; 2315983DNA:polymorphism: :rs780094 (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gckr  (glucokinase regulator)

Genes (Mus musculus)
Gckr  (glucokinase regulatory protein)

Genes (Homo sapiens)
GCKR  (glucokinase regulator)


Additional Information