Common genetic variants of the human steroid 21-hydroxylase gene (CYP21A2) are related to differences in circulating hormone levels

Márton Doleschall, Julianna A nna Szabó, Júlia Pázmándi, Ágnes Szilágyi, Klára Koncz, H. Farkas, Miklós Tóth, P. Igaz, E. Gláz, Z. Prohászka, Márta Korbonits, K. Rácz, G. Füst, A. Patócs

Research output: Contribution to journalArticle

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Abstract

PURPOSE: Systematic evaluation of the potential relationship between the common genetic variants of CYP21A2 and hormone levels.

METHODS: The relationships of CYP21A2 intron 2 polymorphisms and haplotypes with diverse baseline and stimulated blood hormone levels were studied in 106 subjects with non-functioning adrenal incidentaloma (NFAI). The rationale for using NFAI subjects is dual: i) their baseline hormone profiles do not differ from those of healthy subjects and ii) hormone levels after stimulation tests are available.

RESULTS: The carriers (N = 27) of a well-defined CYP21A2 haplotype cluster (c5) had significantly elevated levels of cortisol (p = 0.0110), and 17-hydroxyprogesterone (p = 0.0001) after ACTH stimulation, and 11-deoxycortisol after metyrapone administration (p = 0.0017), but the hormone values were in normal ranges. In addition, the carriers (N = 33) of the C allele of the rs6462 polymorphism had a higher baseline aldosterone level (p = 0.0006). The prevalence of these genetic variants of CYP21A2 did not differ between NFAI and healthy subjects.

CONCLUSIONS: The common CYP21A2 variants presumably exert the same effect on hormone levels in the healthy and disease-affected populations. Therefore, they may contribute to complex diseases such as some cardiovascular diseases, and may influence the genotype-phenotype correlation in patients with congenital adrenal hyperplasia (CAH) including the individual need for hormone substitution.

Original languageEnglish
Pages (from-to)e107244
JournalPLoS One
Volume9
Issue number9
DOIs
Publication statusPublished - 2014

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Steroid 21-Hydroxylase
Medical Genetics
steroids
Genes
hormones
Hormones
genes
Polymorphism
Haplotypes
Healthy Volunteers
haplotypes
17-hydroxyprogesterone
metyrapone
Cortodoxone
genetic polymorphism
17-alpha-Hydroxyprogesterone
Metyrapone
Congenital Adrenal Hyperplasia
aldosterone
corticotropin

ASJC Scopus subject areas

  • Medicine(all)

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Common genetic variants of the human steroid 21-hydroxylase gene (CYP21A2) are related to differences in circulating hormone levels. / Doleschall, Márton; Szabó, Julianna A nna; Pázmándi, Júlia; Szilágyi, Ágnes; Koncz, Klára; Farkas, H.; Tóth, Miklós; Igaz, P.; Gláz, E.; Prohászka, Z.; Korbonits, Márta; Rácz, K.; Füst, G.; Patócs, A.

In: PLoS One, Vol. 9, No. 9, 2014, p. e107244.

Research output: Contribution to journalArticle

Doleschall, Márton ; Szabó, Julianna A nna ; Pázmándi, Júlia ; Szilágyi, Ágnes ; Koncz, Klára ; Farkas, H. ; Tóth, Miklós ; Igaz, P. ; Gláz, E. ; Prohászka, Z. ; Korbonits, Márta ; Rácz, K. ; Füst, G. ; Patócs, A. / Common genetic variants of the human steroid 21-hydroxylase gene (CYP21A2) are related to differences in circulating hormone levels. In: PLoS One. 2014 ; Vol. 9, No. 9. pp. e107244.
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abstract = "PURPOSE: Systematic evaluation of the potential relationship between the common genetic variants of CYP21A2 and hormone levels.METHODS: The relationships of CYP21A2 intron 2 polymorphisms and haplotypes with diverse baseline and stimulated blood hormone levels were studied in 106 subjects with non-functioning adrenal incidentaloma (NFAI). The rationale for using NFAI subjects is dual: i) their baseline hormone profiles do not differ from those of healthy subjects and ii) hormone levels after stimulation tests are available.RESULTS: The carriers (N = 27) of a well-defined CYP21A2 haplotype cluster (c5) had significantly elevated levels of cortisol (p = 0.0110), and 17-hydroxyprogesterone (p = 0.0001) after ACTH stimulation, and 11-deoxycortisol after metyrapone administration (p = 0.0017), but the hormone values were in normal ranges. In addition, the carriers (N = 33) of the C allele of the rs6462 polymorphism had a higher baseline aldosterone level (p = 0.0006). The prevalence of these genetic variants of CYP21A2 did not differ between NFAI and healthy subjects.CONCLUSIONS: The common CYP21A2 variants presumably exert the same effect on hormone levels in the healthy and disease-affected populations. Therefore, they may contribute to complex diseases such as some cardiovascular diseases, and may influence the genotype-phenotype correlation in patients with congenital adrenal hyperplasia (CAH) including the individual need for hormone substitution.",
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AU - Doleschall, Márton

AU - Szabó, Julianna A nna

AU - Pázmándi, Júlia

AU - Szilágyi, Ágnes

AU - Koncz, Klára

AU - Farkas, H.

AU - Tóth, Miklós

AU - Igaz, P.

AU - Gláz, E.

AU - Prohászka, Z.

AU - Korbonits, Márta

AU - Rácz, K.

AU - Füst, G.

AU - Patócs, A.

PY - 2014

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N2 - PURPOSE: Systematic evaluation of the potential relationship between the common genetic variants of CYP21A2 and hormone levels.METHODS: The relationships of CYP21A2 intron 2 polymorphisms and haplotypes with diverse baseline and stimulated blood hormone levels were studied in 106 subjects with non-functioning adrenal incidentaloma (NFAI). The rationale for using NFAI subjects is dual: i) their baseline hormone profiles do not differ from those of healthy subjects and ii) hormone levels after stimulation tests are available.RESULTS: The carriers (N = 27) of a well-defined CYP21A2 haplotype cluster (c5) had significantly elevated levels of cortisol (p = 0.0110), and 17-hydroxyprogesterone (p = 0.0001) after ACTH stimulation, and 11-deoxycortisol after metyrapone administration (p = 0.0017), but the hormone values were in normal ranges. In addition, the carriers (N = 33) of the C allele of the rs6462 polymorphism had a higher baseline aldosterone level (p = 0.0006). The prevalence of these genetic variants of CYP21A2 did not differ between NFAI and healthy subjects.CONCLUSIONS: The common CYP21A2 variants presumably exert the same effect on hormone levels in the healthy and disease-affected populations. Therefore, they may contribute to complex diseases such as some cardiovascular diseases, and may influence the genotype-phenotype correlation in patients with congenital adrenal hyperplasia (CAH) including the individual need for hormone substitution.

AB - PURPOSE: Systematic evaluation of the potential relationship between the common genetic variants of CYP21A2 and hormone levels.METHODS: The relationships of CYP21A2 intron 2 polymorphisms and haplotypes with diverse baseline and stimulated blood hormone levels were studied in 106 subjects with non-functioning adrenal incidentaloma (NFAI). The rationale for using NFAI subjects is dual: i) their baseline hormone profiles do not differ from those of healthy subjects and ii) hormone levels after stimulation tests are available.RESULTS: The carriers (N = 27) of a well-defined CYP21A2 haplotype cluster (c5) had significantly elevated levels of cortisol (p = 0.0110), and 17-hydroxyprogesterone (p = 0.0001) after ACTH stimulation, and 11-deoxycortisol after metyrapone administration (p = 0.0017), but the hormone values were in normal ranges. In addition, the carriers (N = 33) of the C allele of the rs6462 polymorphism had a higher baseline aldosterone level (p = 0.0006). The prevalence of these genetic variants of CYP21A2 did not differ between NFAI and healthy subjects.CONCLUSIONS: The common CYP21A2 variants presumably exert the same effect on hormone levels in the healthy and disease-affected populations. Therefore, they may contribute to complex diseases such as some cardiovascular diseases, and may influence the genotype-phenotype correlation in patients with congenital adrenal hyperplasia (CAH) including the individual need for hormone substitution.

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