Studies of variability in the PTEN gene among Danish caucasian patients with Type II diabetes mellitus.
OBJECTIVE
Phosphatase and tensin homologue deleted from chromosome ten (PTEN) has recently been characterized as a novel member in the expanding network of proteins regulating the intracellular effects of insulin. By dephosphorylation of phosphatidyl-inositol-(3, 4, 5)-trisphosphate (PIP3) the PTEN protein regulates the insulin-dependent phosphoinositide 3-kinase (PI3K) signalling cassette and accordingly might function as a regulator of insulin sensitivity in skeletal muscle and adipose tissue. In this study we tested PTEN as a candidate gene for insulin resistance and late-onset Type II (non-insulin-dependent) diabetes mellitus in a Danish Caucasian population.


METHODS
The nine exons of the PTEN, including intronic flanking regions were analysed by PCR-SSCP and heteroduplex analysis in 62 patients with insulin-resistant Type II diabetes.


RESULTS
No mutations predicted to influence the expression or biological function of the PTEN protein but four intronic polymorphisms were identified: IVS1-96 A-->G (allelic frequency 0.22, 95 % CI: 0.12-0.32), IVS3 + 99 C-->T (0.01, CI: 0-0.03), IVS7-3 TT-->T (0.10, CI: 0.03-0.18) and IVS8 + 32 G-->T (0.35, CI: 0.23-0.47). The IVS8 + 32 G-->T polymorphism was used as a bi-allelic marker for the PTEN locus and examined in 379 patients with Type II diabetes and in 224 control subjects with normal glucose tolerance. The IVS8 + 32 G-->T polymorphism in the PTEN was not associated with Type II diabetes and it did not have any effect on body-mass index, blood pressure, HOMA insulin resistance index, or concentrations of plasma glucose, serum insulin or serum C peptide obtained during an oral glucose tolerance test (OGTT).


CONCLUSIONS
Variability in the PTEN is not a common cause of Type II diabetes in the Danish Caucasian population.
Steno Diabetes Center and Hagedorn Research Institute, Copenhagen, Denmark.
L
L
Hansen
J N
JN
Jensen
C T
CT
Ekstrøm
H
H
Vestergaard
T
T
Hansen
O
O
Pedersen
D000273:Adipose Tissue / Q000187:drug effects; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D002096:C-Peptide / Q000097:blood; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005091:Exons; D005215:Fasting; D005787:Gene Frequency; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000502:physiology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D025521:Tumor Suppressor Proteins; D044465:White People
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D010744:Phosphoric Monoester Hydrolases; D025521:Tumor Suppressor Proteins; C060974:phosphatidylinositol 3,4,5-triphosphate; C494929:PTEN protein, human