Promoter polymorphisms -359T/C and -303A/G of the catalytic subunit p110beta gene of human phosphatidylinositol 3-kinase are not associated with insulin secretion or insulin sensitivity in finnish subjects.
OBJECTIVE
Phosphatidylinositol (PI) 3-kinase activity is required for insulin-stimulated translocation of GLUT4 transporters and glucose uptake and utilization. Therefore, genes encoding the subunits of PI 3-kinase are promising candidate genes for insulin resistance and type 2 diabetes. We recently cloned the catalytic subunit p110beta gene of human PI 3-kinase and reported two nucleotide polymorphisms, -359T/C and -303A/G, in the promoter region of this gene. In this study, we determined the effects of these polymorphisms on insulin secretion and insulin sensitivity.


METHODS
We studied two separate groups of Finnish nondiabetic subjects. Insulin secretion was evaluated by intravenous glucose tolerance test and insulin sensitivity by hyperinsulinemic-euglycemic clamp.


RESULTS
Our results showed that the -359T/C and -303A/G polymorphisms did not have a significant effect on fasting plasma insulin levels, insulin secretion, or insulin sensitivity.


CONCLUSIONS
It is unlikely that the promoter polymorphisms -359T/C and -303A/G of the catalytic subunit p110beta gene of human PI 3-kinase have a major impact on insulin secretion, insulin sensitivity, or the risk of type 2 diabetes in Finnish subjects.
Kossila
Maija
M
A.I. Virtanen Institute for Molecular Sciences, Kuopio. Department of Medicine, University of Kuopio, Kuopio, Finland.
Pihlajamäki
Jussi
J
Kärkkäinen
Päivi
P
Miettinen
Raija
R
Kekäläinen
Päivi
P
Vauhkonen
Ilkka
I
Ylä-Herttuala
Seppo
S
Laakso
Markku
M
D000328:Adult; D015992:Body Mass Index; D020134:Catalytic Domain / Q000235:genetics; D005260:Female; D005387:Finland; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics*; D000078790:Insulin Secretion; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics
D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases