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Objectives

Diabetes mellitus type 2 (DM-2) is a complex disorder with a strong genetic background. Protein tyrosine phosphatase-1B (PTP-1B) dephosphorylates various receptor protein kinases in vitro, including the beta subunit of the insulin receptor, therefore representing a potential candidate to be involved in the polygenic pathogenesis of DM-2. Recently a Pro387Leu variant of the PTP-1B gene has been associated with an increased risk of DM-2 in a Danish population. Reports from China and Finland failed to confirm this association.

Design, setting and subjects

The purpose of the present study was to examine the possible association between the presence of DM-2 and the Pro387Leu polymorphism in a German Caucasian population. A total of 836 subjects (age 20-92 years) participated in the study. The presence of the Pro387Leu variant of the PTP-1B gene was investigated using polymerase chain reaction (PCR) restriction fragment-length polymorphism in 402 subjects with DM-2 (231 men, 171 women, age 63.1 +/- 10.8 years, BMI 28.7 +/-5.1 kg m(-2)) and in 434 normoglycemic age- and sex-matched control subjects (248 men, 186 women, age 64.4 +/-6.5 years, BMI 26.5 +/-3.7 kg m(-2)).

Results

Nine subjects in the control group and nine in the diabetic group (allelic frequency 0.99% in both groups) carried the Pro387Leu polymorphism. A meta-analysis on published data of >3000 subjects including our own data did not find an association between the polymorphism and DM-2. In addition, the polymorphism had no significant influence on the presence of atherosclerotic disease, whilst the influence of other known cardiovascular risk factors was confirmed. Furthermore, the impact of the mutation on metabolic and anthropometric parameters in both groups was examined. Amongst the controls there were no significant differences in BMI, HDL and LDL cholesterol or blood pressure between the two groups with or without the Pro387Leu polymorphism. The same was true for the diabetic group. Interestingly, in both diabetics and controls, Pro387Leu carriers had significantly higher triglycerides. In a logistic regression model only BMI and family history but not polymorphism were predictors of DM-2.

Conclusions

In conclusion, the present data suggest that in a German Caucasian population the Pro387Leu polymorphism of the PTP-1B gene is not associated with DM-2 but may play a role in other metabolic phenotypes."xsd:string
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http://purl.uniprot.org/citations/15715684http://purl.uniprot.org/core/author"Kotzka J."xsd:string
http://purl.uniprot.org/citations/15715684http://purl.uniprot.org/core/author"Krone W."xsd:string
http://purl.uniprot.org/citations/15715684http://purl.uniprot.org/core/author"Muller-Wieland D."xsd:string
http://purl.uniprot.org/citations/15715684http://purl.uniprot.org/core/author"Faust M."xsd:string
http://purl.uniprot.org/citations/15715684http://purl.uniprot.org/core/author"Giannakidou E."xsd:string
http://purl.uniprot.org/citations/15715684http://purl.uniprot.org/core/author"Berthold H.K."xsd:string
http://purl.uniprot.org/citations/15715684http://purl.uniprot.org/core/author"Gouni-Berthold I."xsd:string
http://purl.uniprot.org/citations/15715684http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/15715684http://purl.uniprot.org/core/name"J Intern Med"xsd:string
http://purl.uniprot.org/citations/15715684http://purl.uniprot.org/core/pages"272-280"xsd:string
http://purl.uniprot.org/citations/15715684http://purl.uniprot.org/core/title"The Pro387Leu variant of protein tyrosine phosphatase-1B is not associated with diabetes mellitus type 2 in a German population."xsd:string
http://purl.uniprot.org/citations/15715684http://purl.uniprot.org/core/volume"257"xsd:string
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