{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T08:59:28Z","timestamp":1768294768233,"version":"3.49.0"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2008,6,28]],"date-time":"2008-06-28T00:00:00Z","timestamp":1214611200000},"content-version":"vor","delay-in-days":3010,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2000,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>OBJECTIVES To test the hypothesis that the triad of hyperandrogenism, insulin resistance and acanthosis nigricans (HAIRAN syndrome) in the presence of obesity, also known as type C insulin resistance, is caused by mutations in the gene for peroxisome proliferator activated receptor \u03b3 (PPAR\u03b3), a receptor for the thiazolidinedione drugs that enhance sensitivity to insulin. To investigate possible correlations between mutations in PPAR\u03b3 and the degree of insulin resistance.<\/jats:p><jats:p>DESIGN A candidate gene approach to study the molecular basis for a syndrome of obesity; a comparison of genotype with <jats:italic>in vivo<\/jats:italic> phenotype. PATIENTS Fifteen unrelated patients with HAIRAN syndrome and obesity. Controls for the gene analysis: 25 unrelated non\u2010diabetic non\u2010obese individuals. Controls for the metabolic studies: six unrelated patients with type 2 diabetes mellitus and nine unrelated non\u2010diabetic non\u2010obese individuals. MEASUREMENTS Analysis of polymerase chain reaction (PCR) products of the 7 exons that constitute the entire coding region of both PPAR\u03b3 isoforms (PPAR\u03b31 and PPAR\u03b32) for single\u2010stranded conforma\u2010tional polymorphisms (SSCP); in exons with variant patterns: restriction fragment length polymorphism (RFLP) analysis; and, where relevant, direct sequencing. Evaluation of insulin resistance using the insulin euglycaemic clamp technique. RESULTS A synonymous substitution in codon 477 (CA<jats:italic>C<\/jats:italic><jats:sup>His<\/jats:sup>\u2190 CAF<jats:sup>His<\/jats:sup>) was found in one patient. A missense mutation in codon 12 of PPAR\u03b32 (<jats:italic>C<\/jats:italic>CA<jats:sup>pro<\/jats:sup>\u2190 GCA<jats:sup>Ala<\/jats:sup>) was found in another patient, but not in any of 25 non\u2010diabetic, non\u2010obese control individuals. The patient with the Pro12Ala variant had the highest steady state glucose infusion rate (SSGIR) and most marked suppression of hepatic glucose production rate (HGPR) of all of the patients studied. CONCLUSIONS Mutations in the PPAR\u03b3 gene are unlikely to be major contributors to HAIRAN syndrome with obesity. 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