Association between the human glycoprotein PC-1 gene and elevated glucose and insulin levels in a paired-sibling analysis

We studied whether there is an association between the single nucleotide po lymorphism c.533A>C (K121Q) in the glycoprotein PC-1 gene and features of t he metabolic syndrome in case-control and intrafamily association studies i n 922 subjects from Finland and Sweden. No difference was observed in the Q allele frequency between control subjects and type 2 diabetic subjects (12 .9 vs. 15.1%), The QK genotype was associated with higher fasting plasma gl ucose (FPG) concentrations than the WC genotype in type 2 diabetic patients (P <0.001) and their relatives (P <0.05). A permutation test of siblings d iscordant for the QK and KK genotypes also showed that the nondiabetic sibl ings with the QK genotype had higher FPG (6.1 +/- 2.0 vs. 5.4 +/- 0.6 mmol/ l, P <0.001) and fasting insulin (7.0 +/- 3.6 vs. 4.8 +/- 2.6 mU/l, P <0.05 ) concentrations than the carriers of the KK genotype. In addition, diabeti c siblings with the QK genotype had higher systolic blood pressure (147.0 /- 18.0 vs. 140.0 +/- 18.7 mmHg, P <0.05) and higher fasting (9.9 +/- 3.0 v s. 8.8 +/- 2.8 mmol/l, P <0.05) and 2-h plasma glucose (17.3 +/- 8.5 vs. 12 .9 +/- 4.2 mmol/l, P < 0.05) concentrations than the diabetic carriers of t he KK genotype. The present study shows that, although the Q allele of the human glycoprotein PC-1 gene is associated with surrogate measures of insul in resistance, it may not be enough to increase the susceptibility to type 2 diabetes.