Aims/hypothesis. 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 obesityrelated 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