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.


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 micro mol x kg(-1) x min(-1), P = 0.012) and nonoxidative glucose disposal (33.71 +/- 10.51 vs. 41.51 +/- 13.36 micro mol x kg(-1) x 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.
Kubaszek
Agata
A
Department of Medicine, University of Kuopio, Finland.
Pihlajamäki
Jussi
J
Karhapää
Pauli
P
Vauhkonen
Ilkka
I
Laakso
Markku
M
D000483:Alleles; D005215:Fasting / Q000097:blood; D005260:Female; D005387:Finland; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006579:Heterozygote; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics* / Q000502:physiology; D000078790:Insulin Secretion; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D011110:Polymorphism, Genetic; D011755:Pyrophosphatases / Q000235:genetics*
D007328:Insulin; D008055:Lipids; D008074:Lipoproteins; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases; D005947:Glucose