Genotypes at 11beta-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.

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 11beta-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.

OBJECTIVE:

The objective of this study was to confirm the postulated digenic inheritance mechanism for ACRD.

DESIGN:

This was a population-based association study (Dallas Heart Study). Subjects were genotyped for the 1971T>G polymorphism in intron 3 of HSD11B1 and the R453Q polymorphism in H6PD.

SUBJECTS:

The study comprised 3551 individuals in a population-based sample (50% black, 35% white, and 15% Hispanic).

MAIN OUTCOME MEASURE:

The main outcome measure was association between genotypes and risk for polycystic ovarian syndrome.

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.

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.

• Authors: Perrin C White
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 90 Issue 10 Pg. 5880-3 (Oct 2005) ISSN: 0021-972X [Print] United States
• PMID: 16091483 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Steroids
• Carbohydrate Dehydrogenases
• galactose-6-phosphate dehydrogenase
• 11-beta-Hydroxysteroid Dehydrogenases
• Cortisone Reductase

Topics

• 11-beta-Hydroxysteroid Dehydrogenases (genetics)
• Adolescent
• Adult
• Aged
• Alleles
• Carbohydrate Dehydrogenases (genetics)
• Cortisone Reductase (deficiency)
• Female
• Gene Frequency
• Genetic Testing
• Genotype
• Humans
• Male
• Middle Aged
• Polycystic Ovary Syndrome (genetics, urine)
• Population
• Risk Factors
• Steroids (urine)
• Texas (epidemiology)