Candidate gene analysis in premature pubarche and adolescent hyperandrogenism.
OBJECTIVE
To identify genetic markers associated with premature pubarche in children and hyperandrogenism in adolescent girls.


METHODS
Association study.


METHODS
Academic research environment.


METHODS
Forty children with premature pubarche (PP), 29 adolescent girls with hyperandrogenism (HA), and 15 healthy control women.


METHODS
None.


METHODS
Genetic variations at five loci selected because of known associations with hyperandrogenism, insulin resistance, hyperinsulinemia, or obesity.


RESULTS
Heterozygosity for CYP21 mutations was identified in 14 of 40 (35%) PP, 8 of 29 (28%) HA, and 1 of 30 (3%) controls. Heterozygosity for HSD3B2 variants was identified in 3 of 40 (7.5%) PP, 5 of 29 (17%) HA, and 0/15 controls. Among the PP, 11 of 80 (14%), 5 of 80 (6%), and 7 of 80 (9%) alleles showed the IRS-1, GRL, and ADRB3 variants, respectively. Among the HA, 5 of 58 (8.6%), 3 of 58 (5%), and 6 of 58 (10%) alleles showed the IRS-1, GRL, and ADRB3 variants, respectively. Among the control participants, variant allele frequency was 1 of 30 (3.3%) for IRS-1, 2 of 30 (6.6%) for GRL, and 2 of 30 (6.6%) for ADRB3.


CONCLUSIONS
Our findings suggest that the development of PP and HA can be associated with the occurrence of multiple sequence variants at five susceptibility loci, especially steroidogenic enzyme genes. This approach offers a novel paradigm to investigate and identify the genetic factors relevant to polycystic ovary syndrome.
Witchel
S F
SF
Division of Pediatric Endocrinology, Children's Hospital of Pittsburgh, University of Pittsburgh, Pennsylvania, Pittsburgh 15213, USA. witches@chplink.chp.edu
Smith
R
R
Tomboc
M
M
Aston
C E
CE
D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000735:Androstenedione / Q000097:blood; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006628:Hirsutism / Q000235:genetics; D006801:Humans; D017588:Hyperandrogenism / Q000097:blood / Q000235:genetics*; D055504:Insulin Receptor Substrate Proteins; D008297:Male; D010750:Phosphoproteins / Q000235:genetics; D011629:Puberty, Precocious / Q000097:blood / Q000235:genetics*; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics; D012016:Reference Values; D013255:Steroid 21-Hydroxylase / Q000235:genetics; D013739:Testosterone / Q000097:blood
D005819:Genetic Markers; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D022702:Receptors, Adrenergic, beta-3; D011965:Receptors, Glucocorticoid; D013739:Testosterone; D000735:Androstenedione; D003577:Cytochrome P-450 Enzyme System; D015096:3-Hydroxysteroid Dehydrogenases; D013255:Steroid 21-Hydroxylase