Evidence for a heterozygote advantage in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
J Clin Endocrinol Metab
; 82(7): 2097-101, 1997 Jul.
Article
em En
| MEDLINE
| ID: mdl-9215278
ABSTRACT
21-Hydroxylase deficiency is one of the most common inherited disorders, with carrier frequencies of approximately 10% in all world populations studied to date. The high prevalence of the mutant gene is probably due to a flanking pseudogene serving as a reservoir for mutations. Despite the potential for a high rate of de novo mutations, a founder effect for specific gene conversions is observed in most populations. We hypothesized that there was a survival advantage to 21-hydroxylase heterozygotes, and here we report endocrinological and molecular investigations to test this hypothesis. We defined 28 carriers and 22 mutation-negative controls by molecular genotyping and determined ACTH-stimulated adrenal hormone responses. We found significantly elevated cortisol responses in the carriers compared to controls (30 min cortisol levels normal, 24.2 +/- 4.6 micrograms/dL; carrier, 28.1 +/- 4.2 micrograms/dL; P < 0.005). Cortisol has a crucial role in maintaining homeostasis, influencing differentiation, suppressing inflammation, and effecting cross-talk among the immune, nervous, and endocrine systems. The brisk cortisol response we have documented in carriers of 21-hydroxylase may enable a rapid return to homeostasis in response to infectious, inflammatory, or other environmental stresses and may protect from inappropriate immune responses, such as autoimmune diseases.
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Base de dados:
MEDLINE
Assunto principal:
Esteroide 21-Hidroxilase
/
Hiperplasia Suprarrenal Congênita
Tipo de estudo:
Risk_factors_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Estados Unidos