title: Association between the human glycoprotein PC-1 gene and elevated glucose and insulin levels in a paired-sibling analysis.
abstract: We studied whether there is an association between the single nucleotide polymorphism c.533A>C (K121Q) in the glycoprotein PC-1 gene and features of the metabolic syndrome in case-control and intrafamily association studies in 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 glucose (FPG) concentrations than the KK genotype in type 2 diabetic patients (P <0.001) and their relatives (P <0.05). A permutation test of siblings discordant for the QK and KK genotypes also showed that the nondiabetic siblings with the QK genotype had higher FPG (6.1 +/- 2.0 vs. 5.4 +/- 0.6 mmo/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, diabetic 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 vs. 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 the KK genotype. The present study shows that, although the Q allele of the human glycoprotein PC-1 gene is associated with surrogate measures of insulin resistance, it may not be enough to increase the susceptibility to type 2 diabetes.
authors.affiliation: Department of Endocrinology, Lund University, Malmö University Hospital, Sweden. harvest.gu@endo.mas.lu.se
authors.forename: H F
authors.initials: HF
authors.lastname: Gu
authors.forename: P
authors.initials: P
authors.lastname: Almgren
authors.forename: E
authors.initials: E
authors.lastname: Lindholm
authors.forename: L
authors.initials: L
authors.lastname: Frittitta
authors.forename: A
authors.initials: A
authors.lastname: Pizzuti
authors.forename: V
authors.initials: V
authors.lastname: Trischitta
authors.forename: L C
authors.initials: LC
authors.lastname: Groop
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism*; D001794:Blood Pressure; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005387:Finland; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000235:genetics*; D007328:Insulin / Q000097:blood*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D009679:Nuclear Family; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D012016:Reference Values; D013548:Sweden
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008562:Membrane Glycoproteins; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases