Polymorphisms in the p450 c17 (17-hydroxylase/17,20-Lyase) and p450 c19 (aromatase) genes: Association with serum sex steroid concentrations and bone mineral density in postmenopausal women

J Somner, S McLellan, J Cheung, Y T Mak, M L Frost, K M Knapp, A S Wierzbicki, M Wheeler, I Fogelman, S H Ralston, G N Hampson

Research output: Contribution to journalArticle

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Abstract

The CYP 17 and CYP 19 genes encode 17alpha-hydroxylase/17,20-lyase and aromatase, respectively, both involved in sex hormone synthesis. We investigated the association between 2 common polymorphisms in 1) the promoter region (T-->C substitution) of CYP 17, and 2) exon 3 (G-->A) of CYP 19, bone mineral density (BMD) and serum androgen/estradiol, in a case-control study of 252 postmenopausal women aged 64.5 +/- 9.2 yr ( mean +/- SD). There was no significant difference in serum estradiol concentrations between cases ( n = 136) and controls ( n = 116). The CYP 19 genotype was significantly associated with serum estradiol ( P = 0.002). Women with the AA genotype had higher serum estradiol concentrations compared with those with the GG genotype ( P = 0.03). In older women, those with the CYP 19 GA and GG genotypes had an increased prevalence of osteoporosis ( P = 0.04) and fractures ( P = 0.003). We found no significant association between CYP 17 genotype and serum androgens and estradiol concentrations. However, a significant association was seen between BMD values at the femoral neck with CYP 17 genotype in cases ( P = 0.04) and in the whole study population (P = 0.012). Subjects with the CC genotype had significantly lower BMD ( mean +/- SD: TT, 0.7 +/- 0.16; CC, 0.6 +/- 0.08 g/cm(2); P = 0.006). In conclusion, both CYP 17 and CYP 19 are candidate genes for osteoporosis in postmenopausal women.

Original languageEnglish
Pages (from-to)344-351
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume89
DOIs
Publication statusPublished - 2004

Keywords

  • BREAST-CANCER RISK
  • OSTEOPOROSIS
  • CYP17
  • MEN
  • DETERMINANTS
  • BIOSYNTHESIS
  • DEFICIENCY
  • FRACTURES
  • GENETICS
  • VARIANTS

Cite this

Polymorphisms in the p450 c17 (17-hydroxylase/17,20-Lyase) and p450 c19 (aromatase) genes: Association with serum sex steroid concentrations and bone mineral density in postmenopausal women. / Somner, J ; McLellan, S ; Cheung, J ; Mak, Y T ; Frost, M L ; Knapp, K M ; Wierzbicki, A S ; Wheeler, M ; Fogelman, I ; Ralston, S H ; Hampson, G N .

In: Journal of Clinical Endocrinology and Metabolism, Vol. 89, 2004, p. 344-351.

Research output: Contribution to journalArticle

Somner, J ; McLellan, S ; Cheung, J ; Mak, Y T ; Frost, M L ; Knapp, K M ; Wierzbicki, A S ; Wheeler, M ; Fogelman, I ; Ralston, S H ; Hampson, G N . / Polymorphisms in the p450 c17 (17-hydroxylase/17,20-Lyase) and p450 c19 (aromatase) genes: Association with serum sex steroid concentrations and bone mineral density in postmenopausal women. In: Journal of Clinical Endocrinology and Metabolism. 2004 ; Vol. 89. pp. 344-351.
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abstract = "The CYP 17 and CYP 19 genes encode 17alpha-hydroxylase/17,20-lyase and aromatase, respectively, both involved in sex hormone synthesis. We investigated the association between 2 common polymorphisms in 1) the promoter region (T-->C substitution) of CYP 17, and 2) exon 3 (G-->A) of CYP 19, bone mineral density (BMD) and serum androgen/estradiol, in a case-control study of 252 postmenopausal women aged 64.5 +/- 9.2 yr ( mean +/- SD). There was no significant difference in serum estradiol concentrations between cases ( n = 136) and controls ( n = 116). The CYP 19 genotype was significantly associated with serum estradiol ( P = 0.002). Women with the AA genotype had higher serum estradiol concentrations compared with those with the GG genotype ( P = 0.03). In older women, those with the CYP 19 GA and GG genotypes had an increased prevalence of osteoporosis ( P = 0.04) and fractures ( P = 0.003). We found no significant association between CYP 17 genotype and serum androgens and estradiol concentrations. However, a significant association was seen between BMD values at the femoral neck with CYP 17 genotype in cases ( P = 0.04) and in the whole study population (P = 0.012). Subjects with the CC genotype had significantly lower BMD ( mean +/- SD: TT, 0.7 +/- 0.16; CC, 0.6 +/- 0.08 g/cm(2); P = 0.006). In conclusion, both CYP 17 and CYP 19 are candidate genes for osteoporosis in postmenopausal women.",
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TY - JOUR

T1 - Polymorphisms in the p450 c17 (17-hydroxylase/17,20-Lyase) and p450 c19 (aromatase) genes: Association with serum sex steroid concentrations and bone mineral density in postmenopausal women

AU - Somner, J

AU - McLellan, S

AU - Cheung, J

AU - Mak, Y T

AU - Frost, M L

AU - Knapp, K M

AU - Wierzbicki, A S

AU - Wheeler, M

AU - Fogelman, I

AU - Ralston, S H

AU - Hampson, G N

PY - 2004

Y1 - 2004

N2 - The CYP 17 and CYP 19 genes encode 17alpha-hydroxylase/17,20-lyase and aromatase, respectively, both involved in sex hormone synthesis. We investigated the association between 2 common polymorphisms in 1) the promoter region (T-->C substitution) of CYP 17, and 2) exon 3 (G-->A) of CYP 19, bone mineral density (BMD) and serum androgen/estradiol, in a case-control study of 252 postmenopausal women aged 64.5 +/- 9.2 yr ( mean +/- SD). There was no significant difference in serum estradiol concentrations between cases ( n = 136) and controls ( n = 116). The CYP 19 genotype was significantly associated with serum estradiol ( P = 0.002). Women with the AA genotype had higher serum estradiol concentrations compared with those with the GG genotype ( P = 0.03). In older women, those with the CYP 19 GA and GG genotypes had an increased prevalence of osteoporosis ( P = 0.04) and fractures ( P = 0.003). We found no significant association between CYP 17 genotype and serum androgens and estradiol concentrations. However, a significant association was seen between BMD values at the femoral neck with CYP 17 genotype in cases ( P = 0.04) and in the whole study population (P = 0.012). Subjects with the CC genotype had significantly lower BMD ( mean +/- SD: TT, 0.7 +/- 0.16; CC, 0.6 +/- 0.08 g/cm(2); P = 0.006). In conclusion, both CYP 17 and CYP 19 are candidate genes for osteoporosis in postmenopausal women.

AB - The CYP 17 and CYP 19 genes encode 17alpha-hydroxylase/17,20-lyase and aromatase, respectively, both involved in sex hormone synthesis. We investigated the association between 2 common polymorphisms in 1) the promoter region (T-->C substitution) of CYP 17, and 2) exon 3 (G-->A) of CYP 19, bone mineral density (BMD) and serum androgen/estradiol, in a case-control study of 252 postmenopausal women aged 64.5 +/- 9.2 yr ( mean +/- SD). There was no significant difference in serum estradiol concentrations between cases ( n = 136) and controls ( n = 116). The CYP 19 genotype was significantly associated with serum estradiol ( P = 0.002). Women with the AA genotype had higher serum estradiol concentrations compared with those with the GG genotype ( P = 0.03). In older women, those with the CYP 19 GA and GG genotypes had an increased prevalence of osteoporosis ( P = 0.04) and fractures ( P = 0.003). We found no significant association between CYP 17 genotype and serum androgens and estradiol concentrations. However, a significant association was seen between BMD values at the femoral neck with CYP 17 genotype in cases ( P = 0.04) and in the whole study population (P = 0.012). Subjects with the CC genotype had significantly lower BMD ( mean +/- SD: TT, 0.7 +/- 0.16; CC, 0.6 +/- 0.08 g/cm(2); P = 0.006). In conclusion, both CYP 17 and CYP 19 are candidate genes for osteoporosis in postmenopausal women.

KW - BREAST-CANCER RISK

KW - OSTEOPOROSIS

KW - CYP17

KW - MEN

KW - DETERMINANTS

KW - BIOSYNTHESIS

KW - DEFICIENCY

KW - FRACTURES

KW - GENETICS

KW - VARIANTS

U2 - 10.1210/jc.2003-030164

DO - 10.1210/jc.2003-030164

M3 - Article

VL - 89

SP - 344

EP - 351

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

ER -