The K121Q Polymorphism of the PC-1 Gene Is Associated With Insulin Resistance but not With Dyslipidemia

Abstract

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 I) 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 I, 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 μmol · kg⁻¹ · min⁻¹, P = 0.012) and nonoxidative glucose disposal (33.71 ± 10.51 vs. 41.51 ± 13.36 μmol · kg⁻¹ · min⁻¹, P = 0.015) during the clamp. In group II, there was no significant difference between the 121Q 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.