Single nucleotide polymorphisms of protein tyrosine phosphatase 1B gene are associated with obesity in morbidly obese French subjects.
OBJECTIVE
The development of insulin resistance may contribute to the occurrence and progression of the metabolic syndrome associated with obesity. Components contributing to the insulin pathway and its regulation are good candidates for the molecular study of metabolic syndrome pathogenesis. Protein tyrosine phosphatase 1B (PTP 1B) is an important negative regulator of insulin. We investigated whether PTP 1B SNPs are associated with obesity and obesity-related traits as well as global metabolic syndrome in morbidly obese subjects.


METHODS
Untranslated and coding regions of the PTP 1B gene were screened in groups of non-diabetic and diabetic obese subjects and in non-obese subjects. Unrelated morbidly obese ( n=711) and non-obese ( n=427) French Caucasian subjects were genotyped for a case-control study.


RESULTS
Six SNPs were identified: two rare variants were located in 5'UTR (-109 C>T and -69 C>T), two in the intronic regions (IVS3+38 G>T and IVS5+3666delT) and two have been described previously (P303P in exon 8 and P387L in exon 9). A case-control study showed an association between the frequent IVS5+3666delT SNP and obesity ( p=0.02). In the obese group, associations between PTP 1B SNPs and features of dyslipidaemia were found. P303P was associated with lower apolipoprotein A1 levels ( p=0.05) whereas P387L was associated with higher triglyceride ( p=0.0003), apolipoprotein B ( p=0.09) and lipoprotein a concentrations ( p=0.006).


CONCLUSIONS
Our results support the hypothesis that the PTP 1B gene contributes to the polygenic basis of obesity. PTP 1B SNPs may interact with environmental factors to induce more severe phenotypes, e.g. atherogenic dyslipidaemia, in morbidly obese subjects.
Kipfer-Coudreau
S
S
INSERM Avenir and EA 3502, Nutrition Department, Paris VI University, Paris, France.
Eberlé
D
D
INSERM Avenir and EA 3502, Nutrition Department, Paris VI University, Paris, France.|INSERM U465, Paris VI University, Paris, France.
Sahbatou
M
M
Centre d'Etude du Polymorphisme Humain, Paris, France.
Bonhomme
A
A
INSERM Avenir and EA 3502, Nutrition Department, Paris VI University, Paris, France.
Guy-Grand
B
B
INSERM Avenir and EA 3502, Nutrition Department, Paris VI University, Paris, France.
Froguel
P
P
CNRS UPRESA 80-90, Lille Institute of Biology, Pasteur Institute, Lille and Hammersmith Genome Centre, Imperial College, London, UK.
Galan
P
P
INSERM/INRA/CNAM, Institut Scientifique et Technique de la Nutrition et de l'Alimentation, ISTNA/CNAM, Paris, France.
Basdevant
A
A
INSERM Avenir and EA 3502, Nutrition Department, Paris VI University, Paris, France.
Clément
K
K
INSERM Avenir and EA 3502, Nutrition Department, Paris VI University, Paris, France. karine.clement@htd.ap-hop-paris.fr.|Hôtel-Dieu Service de Nutrition, 1 place du parvis Nôtre-Dame, 75181, Paris Cedex 04, France. karine.clement@htd.ap-hop-paris.fr.
D002784:Cholesterol / Q000097:blood; D017931:DNA Primers; D005602:France; D005820:Genetic Testing / Q000379:methods; D014644:Genetic Variation; D006801:Humans; D009767:Obesity, Morbid / Q000201:enzymology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
D017931:DNA Primers; D014280:Triglycerides; D002784:Cholesterol; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases