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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Demirci
F Y
FY
Department of Human Genetics, University of Pittsburgh, PA 15261, USA. fyd1@pitt.edu
Dressen
A S
AS
Hamman
R F
RF
Bunker
C H
CH
Kammerer
C M
CM
Kamboh
M I
MI
D044383:Black People / Q000235:genetics; D001786:Blood Glucose / Q000032:analysis*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005215:Fasting; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation / Q000502:physiology*; D005838:Genotype; D005952:Glucose-6-Phosphatase / Q000235:genetics*; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood; D044465:White People / Q000235:genetics
D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D002784:Cholesterol; D005952:Glucose-6-Phosphatase; C492194:G6PC2 protein, human