Common single nucleotide polymorphisms in intron 3 of the calpain-10 gene influence hirsutism.
OBJECTIVE
To study three common polymorphisms in intron 3 of the calpain-10 gene (CAPN10) in hyperandrogenic patients.


METHODS
Case-control study.


METHODS
Academic hospital.


METHODS
Ninety-seven hyperandrogenic patients and 37 healthy controls.


METHODS
Basal and adrenocorticotropin-stimulated serum samples and genomic DNA samples were obtained during the follicular phase of the menstrual cycle.


METHODS
Genotyping of the UCSNP43, UCSNP44, and UCSNP45 polymorphisms in CAPN10 and serum androgen levels.


RESULTS
Sixteen patients had idiopathic hirsutism, defined as normal serum androgen levels and regular menstrual cycles. Eighty-one hyperandrogenic patients (those presenting with hyperandrogenemic hirsutism or the polycystic ovary syndrome) were analyzed further. UCSNP45 alleles were distributed differently among the study groups. Heterozygosity for the uncommon C allele was increased in patients with idiopathic hirsutism (31.3%) and reduced in hyperandrogenic patients (7.4%) compared with controls (16.2%). The UCSNP44 and UCSNP43 alleles were in linkage disequilibrium, and were distributed equally among patients with idiopathic hirsutism, hyperandrogenism, and controls. However, the uncommon A allele at UCSNP43 was associated with higher hirsutism score (mean [+/- SD], 9.9 +/- 6.8, 12.7 +/- 7.7, and 14.6 +/- 8.2 in GG, GA, and AA participants, respectively). No other differences were observed in clinical and biochemical characteristics, including insulin sensitivity, by CAPN10 variant.


CONCLUSIONS
The C allele at the UCSNP45 locus in CAPN10 is associated with idiopathic hirsutism, and UCSNP43 influences the hirsutism score.
Escobar-Morreale
Héctor F
HF
Department of Endocrinology, Hospital Ramón y Cajal, Madrid, Spain. hector.escobar@uam.es
Peral
Belén
B
Villuendas
Gemma
G
Calvo
Rosa M
RM
Sancho
José
J
San Millán
José L
JL
D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage; D000328:Adult; D002154:Calpain / Q000235:genetics*; D016022:Case-Control Studies; D003350:Cortodoxone / Q000097:blood; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005260:Female; D005498:Follicular Phase; D006628:Hirsutism / Q000235:genetics*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007438:Introns / Q000235:genetics / Q000502:physiology; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000502:physiology*; D017422:Sequence Analysis, DNA; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000097:blood
D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; D004247:DNA; D002154:Calpain; C415197:calpain 10; D003350:Cortodoxone; D006854:Hydrocortisone