Glucose and lipid metabolism in relation to novel polymorphisms in the 5′-AMP-activated protein kinase γ2 gene in Chinese

The 5′-AMP-activated protein kinase (AMPK) behaves as a fuel sensor in glucose and lipid metabolism. We sequenced exon 1 and flanking regions of the gene encoding for the γ2 subunit of AMPK (AMPKγ2) and identified two novel common polymorphisms at position −26 and IVS1 + 43. We then studied these two polymorphisms in relation to plasma glucose, insulin resistance, β-cell function, and serum lipids in 290 Han Chinese undergoing an oral glucose tolerance test and a frequently sampled intravenous glucose tolerance test. The −26C/T and IVS1 + 43C/T polymorphisms were in tight linkage disequilibrium (P = 0.0002). In adjusted categorical analyses, the −26TT genotype tended to be associated with a higher risk of type 2 diabetes (odds ratio 4.52, P = 0.07). The adjusted continuous analyses were confirmatory. −26TT subjects, compared with −26C allele carriers, had higher concentrations of plasma glucose, both fasting (7.3 vs. 6.1 mmol/L, P = 0.02) and after oral glucose loading (area under the curve for glucose, 1984 vs. 1596 min mmol/L, P = 0.002), and had lower acute insulin response to glucose (143 vs. 404, P = 0.0005) and disposition index (151 vs. 459, P = 0.008). In further adjusted analyses, we observed that IVS1 + 43TT subjects, compared with IVS1 + 43C allele carriers, had significantly higher serum concentrations of triglycerides (4.20 vs. 2.00 mmol/L, P < 0.0001) and total cholesterol (5.88 vs. 4.99 mmol/L, P = 0.01). In conclusion, in Chinese, the AMPKγ2 polymorphisms might be associated with glucose and lipid metabolism.