The K121Q polymorphism of the PC-1 gene is associated with insulin resistance but not with dyslipidemia

OBJECTIVE - To investigate the relationship of the K121Q polymorphism of the plasma cell glycoprotein 1 (PC-1) gene with insulin resistance, insulin secretion, and lipids and lipoproteins. RESEARCH DESIGN AND METHODS - Altogether, 110 normoglycemic subjects (group 1) underwent a hyperinsulinemic-euglycemic clamp for evaluation of insulin sensitivity. The first-phase insulin secretion was determined by the intravenous glucose tolerance test (IVGTT) in a separate sample of 295 normoglycemic subjects (group II). RESULTS - The 121Q allele (genotypes K121Q and Q121Q) compared with the K121K genotype was related to higher fasting insulin levels (group I: 69.6 +/- 45.6 vs. 51.9 +/- 28.4 pmol/l [mean +/- SD], P = 0.050; group II: 66.6 +/- 38.8 vs. 53.8 +/- 26.6 pmol/l, P = 0.009). In group 1, subjects carrying the 121Q allele compared with subjects with the K121K genotype had lower rates of whole-body glucose uptake (51.17 +/- 12.07 vs. 60.12 +/- 14.86 mumol (.) kg(-1) (.) min(-1), P = 0.012) and nonoxidative glucose disposal (33.71 +/- 10.51 vs. 41.51 +/- 13.36 mumol (.) kg(-1) (.) min(-1), P = 0.015) during the clamp. In group 11, there was no significant difference between the 12 IQ allele carriers and subjects with the K121K genotype in total first-phase insulin secretion during the first 10 min of the IVGTT (2,973 +/- 2,224 vs. 2,520 +/- 1,492 pmol (.) l(-1) (.) min(-1), P = 0.415). No association of the K121Q polymorphism with serum lipids and lipoproteins was found. CONCLUSIONS - in healthy normoglycemic Finnish subjects, the K121Q polymorphism of the PC-1 gene is associated with insulin resistance but not with impaired insulin secretion or dyslipidemia.