ANALYSIS OF THE INSULIN-RECEPTOR GENE TYROSINE KINASE DOMAIN IN OBESEPATIENTS WITH HYPERANDROGENISM, INSULIN-RESISTANCE AND ACANTHOSIS NIGRICANS (TYPE-C INSULIN-RESISTANCE)

OBJECTIVE: To test the hypothesis that the triad of hyperandrogenism, insulin resistance and acanthosis nigricans (HAIR-AN syndrome) in the presence of obesity, also known as type C insulin resistance (type C), is caused by mutations at the tyrosine kinase domain of the insulin r eceptor gene. DESIGN: A candidate gene approach to study the molecular basis for a syndrome of obesity. SUBJECTS: 15 patients with type C in sulin resistance and 25 control individuals. MEASUREMENTS: Analysis of polymerase chain reaction (PCR) products of exons 17 to 21 of the ins ulin receptor gene, comprising the tyrosine kinase domain, for single strand conformational polymorphisms (SSCP) and sequence analysis of ex ons with variant SSCP patterns. RESULTS: A synonymous C to T substitut ion in position 3 of codon 984, which does not alter the amino acid pr edicted, was found in one patient and in four of 25 control individual s. CONCLUSION: Type C insulin resistance is not commonly caused by mut ations in the tyrosine kinase domain of the insulin receptor gene.