Additive Effects of Genetic Variation in GCK and G6PC2 on Insulin Secretion and Fasting Glucose
Adult
Blood Glucose
Male
0301 basic medicine
0303 health sciences
Genetic Variation
Fasting
Middle Aged
Protein Serine-Threonine Kinases
Polymorphism, Single Nucleotide
Germinal Center Kinases
03 medical and health sciences
Insulin-Secreting Cells
Insulin Secretion
Mexican Americans
Glucose-6-Phosphatase
Humans
Insulin
Original Article
Female
Aged
DOI:
10.2337/db09-0228
Publication Date:
2009-09-10T01:47:25Z
AUTHORS (15)
ABSTRACT
OBJECTIVE
Glucokinase (GCK) and glucose-6-phosphatase catalytic subunit 2 (G6PC2) regulate the glucose-cycling step in pancreatic β-cells and may regulate insulin secretion. GCK rs1799884 and G6PC2 rs560887 have been independently associated with fasting glucose, but their interaction on glucose-insulin relationships is not well characterized.
RESEARCH DESIGN AND METHODS
We tested whether these variants are associated with diabetes-related quantitative traits in Mexican Americans from the BetaGene Study and attempted to replicate our findings in Finnish men from the METabolic Syndrome in Men (METSIM) Study.
RESULTS
rs1799884 was not associated with any quantitative trait (corrected P > 0.1), whereas rs560887 was significantly associated with the oral glucose tolerance test 30-min incremental insulin response (30′ Δinsulin, corrected P = 0.021). We found no association between quantitative traits and the multiplicative interaction between rs1799884 and rs560887 (P > 0.26). However, the additive effect of these single nucleotide polymorphisms was associated with fasting glucose (corrected P = 0.03) and 30′ Δinsulin (corrected P = 0.027). This additive association was replicated in METSIM (fasting glucose, P = 3.5 × 10−10 30′ Δinsulin, P = 0.028). When we examined the relationship between fasting glucose and 30′ Δinsulin stratified by GCK and G6PC2, we noted divergent changes in these quantitative traits for GCK but parallel changes for G6PC2. We observed a similar pattern in METSIM.
CONCLUSIONS
Our data suggest that variation in GCK and G6PC2 have additive effects on both fasting glucose and insulin secretion.
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