PTPN1 polymorphisms are associated with total and low-density lipoprotein cholesterol
Received 1 December 2008; accepted 20 April 2009.
Background
The protein tyrosine phosphatase nonreceptor type 1 (PTPN1) gene encodes for the protein tyrosine phosphatase 1B, which suppresses the signaling pathway of insulin. Variations in PTPN1 may lead to changes in insulin sensitivity and consequent changes in protein tyrosine phosphatase 1B activity may also contribute to the development of metabolic endophenotypes. Our aim was to investigate the association between single nucleotide polymorphisms (SNPs) of the PTPN1 gene and metabolic endophenotypes and insulin sensitivity.
Design and methods
We used data from a population-based cross-sectional study of 382 Dutch Caucasian men aged between 40–80 years, in whom we genotyped and analyzed four tag SNPs in PTPN1.
Results
We show that the minor alleles of three tag SNPs of the PTPN1 gene (rs6067484, rs6020611, rs1060402) are associated with higher levels of total plasma cholesterol and low-density lipoprotein (LDL) cholesterol in men with a body mass index (BMI) below 26kg/m2 (P<0.05). We also show that men with a BMI below 26kg/m2 and carrying the rs3487348T allele tend to have a more beneficial profile for total plasma cholesterol and LDL cholesterol (P<0.05). Haplotypes that comprised these alleles were also borderline statistically significant associated with higher levels of LDL and total cholesterol in men with BMI below 26kg/m2.
Conclusion
Our results suggest that SNPs in the PTPN1 gene are associated with total plasma and LDL cholesterol levels.
aDepartment of Medical Genetics-DBG, Complex Genetics Section
bJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht
cDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Correspondence to Professor Yvonne T. van der Schouw, PhD, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Room STR 6.131, P O Box 85500, Utrecht 3508 GA, The Netherlands Tel: +31 88 755 9360; fax: +31 88 756 8099;
ABSTRACT