Specific CAPN10 gene haplotypes influence the clinical profile of polycystic ovary patients.
Recently, several research groups have evaluated CAPN10 gene in polycystic ovarian syndrome (PCOS) patients and other phenotypes, including hirsutism or intermediate phenotypes of PCOS. Molecular genetic analysis of CAPN10 gene indicates that different alleles may play a role in PCOS susceptibility and could be associated with idiopathic hirsutism. However, these observations are not exempt from controversy, because independent studies cannot replicate these preliminary findings. We present a haplotype-phenotype correlation study of CAPN10 haplotypes in 148 women showing ecographically detected polycystic ovaries (PCO) combined with one or more of these clinical symptoms: amenorrhea or severe oligomenorrhea, hyperandrogenism, and anovulatory infertility, as well as 93 unrelated controls. We have reconstructed and analyzed 482 CAPN10 haplotypes in patients and controls. We detected the association of UCSNP-44 allele with PCO phenotype in the Spanish population (P = 0.02). In addition, we identified several CAPN10 alleles associated to phenotypic differences observed between PCO patients, such as the presence of hypercholesterolemia (haplotype 1121, P = 0.005), presence of hyperandrogenic features (P = 0.05), and familial cancer incidence (haplotype 1111, P = 0.0005). Our results confirm the association of UCSNP-44 allele with PCO phenotype in the Spanish population. Moreover, we have identified novel candidate risk alleles and genotypes, within CAPN10 gene, that could be associated with important phenotypic and prognosis differences observed in PCOS patients.
Gonzalez
Alejandro
A
Centro Avanzado de Fertilidad, Unidad de Reproducción y Genética Humana, Instituto Medico Serman, 11405 Jerez de la Frontera, Cádiz, Spain. alejandro@caf-jerez.com
Abril
Eduardo
E
Roca
Alfredo
A
Aragón
Maria José
MJ
Figueroa
Maria José
MJ
Velarde
Pilar
P
Ruiz
Rocío
R
Fayez
Omar
O
Galán
José Jorge
JJ
Herreros
José Antonio
JA
Real
Luis Miguel
LM
Ruiz
Agustín
A
D000568:Amenorrhea / Q000453:epidemiology / Q000235:genetics; D002154:Calpain / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006239:Haplotypes; D006801:Humans; D017588:Hyperandrogenism / Q000453:epidemiology / Q000235:genetics; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors
D002784:Cholesterol; D002154:Calpain; C415197:calpain 10