Dataset Information

Association of a common G6PC2 variant with fasting plasma glucose levels in non-diabetic individuals.

ABSTRACT: Fasting plasma glucose (FPG) levels correlate with cardiovascular disease and mortality in both diabetic and non-diabetic subjects. G6PC2 encodes a pancreatic islet-specific glucose-6-phosphatase-related protein and G6pc2-null mice were reported to exhibit decreased blood glucose levels. Two recent genome-wide association studies have implicated a role for G6PC2 in regulation of FPGlevels in the general European population and reported the strongest association with the rs560887 SNP. The purpose of this study was to replicate this association in our independent epidemiological samples.DNA samples from non-Hispanic white Americans (NHWs; n = 623), Hispanic Americans (n = 410) and black Africans (n = 787) were genotyped for rs560887 using TaqMan allelic discrimination.While no minor allele A of rs560887 was observed among blacks, its frequency was 33% in NHWs and 17.5% in Hispanics. The rs560887 minor allele was associated with reduced FPG levels in non-diabetic NHWs (p = 0.002 under an additive model). A similar trend of association was observed in non-diabetic Hispanics (p = 0.076 under a dominant model), which was more pronounced in normoglycemic subjects (p = 0.036).Our results independently confirm the robust association of G6PC2/rs560887 with FPG levels in non-diabetic NHWs. The observed evidence for association in Hispanics warrants further studies in larger samples.

SUBMITTER: Demirci FY

PROVIDER: S-EPMC2855271 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Association of a common G6PC2 variant with fasting plasma glucose levels in non-diabetic individuals.

Demirci F Y FY Dressen A S AS Hamman R F RF Bunker C H CH Kammerer C M CM Kamboh M I MI

Annals of nutrition & metabolism 20091218 1

<h4>Background/aims</h4>Fasting plasma glucose (FPG) levels correlate with cardiovascular disease and mortality in both diabetic and non-diabetic subjects. G6PC2 encodes a pancreatic islet-specific glucose-6-phosphatase-related protein and G6pc2-null mice were reported to exhibit decreased blood glucose levels. Two recent genome-wide association studies have implicated a role for G6PC2 in regulation of FPGlevels in the general European population and reported the strongest association with the r ...[more]

PMID: 20029179

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Project description:To collectively evaluate the association of glucose-6-phosphatase catalytic unit 2 (G6PC2) allele variants with elevated fasting glucose (FG) and type 2 diabetes (T2D).Meta-analysis.PubMed, Web of Knowledge and Embase databases.Full text articles of studies that identified an association of G6PC2 with T2D and elevated FG.There was no T2D patient involvement in the analyses on the association of FG with G6PC2, there were T2D patients and non-diabetes patient involvement in the analyses on the association of T2D with G6PC2.Random-effects meta-analyses were used to calculate the pool effect sizes. I2 metric and H2 tests were used to calculate the heterogeneity. Begg's funnel plot and Egger's linear regression test were done to assess publication bias.Of the 423 studies identified, 21 were eligible and included. Data on three loci (rs560887, rs16856187 and rs573225) were available. The G allele at rs560887 in three ethnicities, the C allele at rs16856187 and the A allele at rs573225 all had a positive association with elevated FG. Per increment of G allele at rs560887 and A allele at rs573225 resulted in a FG 0.070 mmol/l and 0.075 mmol/l higher (ß (95% CI) = 0.070 (0.060, 0.079), p = 4.635e-50 and 0.075 (0.065, 0.085), p = 5.856e-48, respectively). With regard to the relationship of rs16856187 and FG, an increase of 0.152 (95% CI: 0.034-0.270; p = 0.011) and 0.317 (95% CI: 0.193-0.442, p = 6.046e-07) was found in the standardized mean difference (SMD) of FG for the AC and CC genotypes, respectively, when compared with the AA reference genotype. However, the G-allele of rs560887 in Caucasians under the additive model and the C-allele of rs16856187 under the allele and dominant models were associated with a decreased risk of T2D (OR (95% CI) = 0.964 (0.947, 0.981), p = 0.570e-4; OR (95% CI) = 0.892 (0.832, 0.956), p = 0.001; and OR (95% CI) = 0.923(0.892, 0.955), p = 5.301e-6, respectively).Our meta-analyses demonstrate that all three allele variants of G6PC2 (rs560887, rs16856187 and rs573225) are associated with elevated FG, with two variants (rs560887 in the Caucasians subgroup and rs16856187 under the allele and dominant model) being associated with T2D as well. Further studies utilizing larger sample sizes and different ethnic populations are needed to extend and confirm these findings.

Dataset Information

Association of a common G6PC2 variant with fasting plasma glucose levels in non-diabetic individuals.

Publications

Association of a common G6PC2 variant with fasting plasma glucose levels in non-diabetic individuals.

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