title: PTPN1 polymorphisms are associated with total and low-density lipoprotein cholesterol.
abstract: 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.
  
  
  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 26 kg/m2 (P<0.05). We also show that men with a BMI below 26 kg/m2 and carrying the rs3487348 T 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 26 kg/m2.
  
  
  CONCLUSIONS
  Our results suggest that SNPs in the PTPN1 gene are associated with total plasma and LDL cholesterol levels.
authors.affiliation: Department of Medical Genetics-DBG, Complex Genetics Section, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Florianne
authors.initials: F
authors.lastname: Bauer
authors.forename: N Charlotte
authors.initials: NC
authors.lastname: Onland-Moret
authors.forename: Onland-Moret N
authors.initials: OM
authors.lastname: Charlotte
authors.forename: Anne G
authors.initials: AG
authors.lastname: Niehoff
authors.forename: Clara C
authors.initials: CC
authors.lastname: Elbers
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Yvonne T
authors.initials: YT
authors.lastname: van der Schouw
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000235:genetics; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D003430:Cross-Sectional Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D016014:Linear Models; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D008875:Middle Aged; D009426:Netherlands; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D055105:Waist Circumference
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D002784:Cholesterol; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1