Additive Effects of Genetic Variation in GCK and G6PC2 on Insulin Secretion and Fasting Glucose

• DOI: 10.2337/db09-0228
• Publication Date: 2009-09-10T01:47:25Z
• Authors: Xia Li; Yu-Hsiang Shu; Anny H. Xiang; Enrique Trigo; Johanna Kuusisto; Jaana Hartiala; Amy J. Swift; Miwa Kawakubo; Heather M. Stringham; Lori L. Bonnycastle; Jean M. Lawrence; Markku Laakso; Hooman Allayee; Thomas A. Buchanan; Richard M. Watanabe
• Keywords: Glucokinase

OBJECTIVE Glucokinase (GCK) and glucose-6-phosphatase catalytic subunit 2 (G6PC2) regulate the glucose-cycling step in pancreatic β-cells may insulin secretion. GCK rs1799884 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 diabetes-related quantitative traits Mexican Americans from BetaGene Study attempted to replicate our findings Finnish men METabolic Syndrome Men (METSIM) Study. RESULTS was any trait (corrected P > 0.1), whereas significantly oral glucose tolerance test 30-min incremental response (30′ Δinsulin, corrected = 0.021). found no association between multiplicative (P 0.26). However, additive effect of single nucleotide polymorphisms 0.03) 30′ Δinsulin 0.027). This replicated METSIM (fasting 3.5 × 10−10 0.028). When we examined relationship stratified by G6PC2, noted divergent changes for parallel G6PC2. observed a similar pattern METSIM. CONCLUSIONS Our data suggest that variation effects both