Lack of association between common polymorphisms in the 17beta-hydroxysteroid dehydrogenase type V gene (HSD17B5) and precocious pubarche.
BACKGROUND
17beta-Hydroxysteroid dehydrogenase (type V; HSD17B5) is a key enzyme involved in testosterone production in females. A single nucleotide polymorphism (SNP) in the promoter region of its gene was recently found to be associated with polycystic ovary syndrome (PCOS) and its related hyperandrogenaemia. Precocious pubarche (PP) is a clinical entity pointing to adrenal androgen excess from mid-childhood onward and is associated with ovarian androgen excess from puberty onward. It is therefore a strong risk factor for PCOS.


METHODS
To investigate associations between this promoter SNP along with three exonic SNPs (one non-synonymous and two synonymous) from the same gene, and PP, a case-control study was performed in 190 girls with PP (84 of which were also tested for functional ovarian hyperandrogenism) from Barcelona, Spain and 71 healthy controls. Clinical features and hormone concentrations relevant to hyperandrogenism were compared by HSD17B5 genotype and haplotype.


RESULTS
Neither HSD17B5 genotypes nor haplotype were associated with PP, or subsequent androgen excess in girls from Barcelona (all P>0.05).


CONCLUSIONS
HSD17B5 SNPs predicted to have functional effects do not appear to be a risk factor for PP in girls from Barcelona, despite these girls being at high risk of developing androgen excess in adulthood.
Petry
Clive J
CJ
Department of Paediatrics, University of Cambridge, Cambridge CB2 2QQ, UK. cjp1002@cam.ac.uk
Ong
Ken K
KK
Wingate
Dianne L
DL
de Zegher
Francis
F
Ibáñez
Lourdes
L
Dunger
David B
DB
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D015096:3-Hydroxysteroid Dehydrogenases; D000074425:Aldo-Keto Reductase Family 1 Member C3; D000728:Androgens / Q000097:blood; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005838:Genotype; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D011629:Puberty, Precocious / Q000201:enzymology / Q000235:genetics*
D000728:Androgens; D017931:DNA Primers; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D006911:Hydroxyprostaglandin Dehydrogenases; C487341:AKR1C3 protein, human; D000074425:Aldo-Keto Reductase Family 1 Member C3