{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:20:24Z","timestamp":1762100424077},"reference-count":16,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,10,1]]},"abstract":"Context: Apparent cortisone reductase deficiency (ACRD) is a rarely ascertained condition characterized by signs of androgen excess in women or children and decreased urinary excretion of cortisol metabolites compared with cortisone metabolites. These findings suggest a deficiency of 11\u03b2-hydroxysteroid dehydrogenase type 1 (11-HSD1; encoded by the HSD11B1 gene), which normally converts cortisone to cortisol. Common polymorphisms in both HSD11B1 and the hexose-6-phosphate dehydrogenase (H6PD) gene encoding hexose-6-phosphate dehydrogenase have been found together in ACRD patients, who carry three of a possible four minor alleles at the two loci.<\/jats:p>\n Objective: The objective of this study was to confirm the postulated digenic inheritance mechanism for ACRD.<\/jats:p>\n Design: This was a population-based association study (Dallas Heart Study). Subjects were genotyped for the 1971T&gt;G polymorphism in intron 3 of HSD11B1 and the R453Q polymorphism in H6PD.<\/jats:p>\n Subjects: The study comprised 3551 individuals in a population-based sample (50% black, 35% white, and 15% Hispanic).<\/jats:p>\n Main Outcome Measure: The main outcome measure was association between genotypes and risk for polycystic ovarian syndrome.<\/jats:p>\n Results: Both polymorphisms occurred more frequently than previously reported. Thus, ACRD genotypes (at least three of four minor alleles) occurred in 7.0% of subjects. There were no associations between genotype and body mass index; waist\/hip ratio; visceral adiposity; measures of insulin sensitivity; levels of testosterone, FSH, or LH (in females); or risk of polycystic ovarian syndrome. There was no genotype effect on urinary free cortisol\/cortisone or corticosteroid metabolite ratios, which were measured in 10 subjects, each carrying zero, three, or four minor alleles.<\/jats:p>\n Conclusions: Previously reported associations of ACRD with HSD11B1 and H6PD alleles represent ascertainment bias. However, rare severe mutations in these genes cannot be ruled out.<\/jats:p>","DOI":"10.1210\/jc.2005-0942","type":"journal-article","created":{"date-parts":[[2005,10,5]],"date-time":"2005-10-05T22:02:56Z","timestamp":1128549776000},"page":"5880-5883","source":"Crossref","is-referenced-by-count":40,"title":["Genotypes at 11\u03b2-Hydroxysteroid Dehydrogenase Type 11B1 and Hexose-6-Phosphate Dehydrogenase Loci Are Not Risk Factors for Apparent Cortisone Reductase Deficiency in a Large Population-Based Sample"],"prefix":"10.1210","volume":"90","author":[{"given":"Perrin C.","family":"White","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9063"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071616263816700_R1","first-page":"3570","article-title":"Apparent cortisone reductase deficiency: a functional defect in 11\u03b2-hydroxysteroid dehydrogenase type 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