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Reproductive Sciences, Vol. 15, No. 3, 305-311 (2008)
DOI: 10.1177/1933719107314064
© 2008 SAGE Publications

A Digenic Combination of Polymorphisms Within ESR1 and ESR2 Genes Are Associated With Age at Menarche in the Spanish Population

Nicolás Mendoza, MD, PhD

Servicio de Ginecología y Obstetricia, Hospital Universitario Virgen de las Nieves, Granada, Spain

Francisco Jesús Morón, MS

Departamento de Genómica Estructural, Neocodex,Avda, Charles Darwin n'6,Acc.A. Parque Tecnológico Isla de la Cartuja, Sevilla, Spain

Francisco Quereda, MD, PhD

Servicio de Ginecología y Obstetricia, Hospital San Juan de Alicante, Alicante, Spain

Francisco Vázquez, MD, PhD

CEOGA, Clínica de Ginecología, Lugo, Spain

Mari C. Rivero

Departamento de Genómica Estructural, Neocodex,Avda, Charles Darwin n'6,Acc.A. Parque Tecnológico Isla de la Cartuja, Sevilla, Spain

Txantón Martínez-Astorquiza, MD, PhD

Servicio de Ginecología, Clínica Sanatorio Bilbaíno, Bilbao, Spain

Luis M. Real, PhD

Departamento de Genómica Estructural, Neocodex,Avda, Charles Darwin n'6,Acc.A. Parque Tecnológico Isla de la Cartuja, Sevilla, Spain

Rafael Sánchez-Borrego, MD, PhD

Clínica Diatros, Gavá, Barcelona, Spain

Antonio González-Pérez, MS

Departamento de Genómica Estructural, Neocodex,Avda, Charles Darwin n'6,Acc.A. Parque Tecnológico Isla de la Cartuja, Sevilla, Spain

Agustín Ruiz, MD, PhD

Departamento de Genómica Estructural, Neocodex,Avda, Charles Darwin n'6,Acc.A. Parque Tecnológico Isla de la Cartuja, Sevilla, Spain, aruiz{at}neocodex.es

In the present study, the authors look at an association of genetic variants within estrogen synthesis and signaling pathways and age at menarche (AAM) in Spanish women. They analyzed 9 polymorphisms in 6 different genes in 714 well-characterized postmenopausal women from Spain. They performed a quantitative trait locus study of these markers individually or in digenic combinations in relation to AAM. None of the studied markers, with the exception of the follicle-stimulating hormone receptor (P = .013), were significantly associated with AAM in the Spanish population, and no marker demonstrated an association of statistical significance after multiple testing corrections ( P > .0055). In contrast, linear regression analysis suggests epistatic interactions including ESR1 and ESR2 loci in relation to AAM in the series (P = .003). The results suggest that epistatic interactions of ESR1 and ESR2 alleles could be associated with advancing AAM among Spanish women.

Key Words: Menarche • SNPs • association studies • complex traits • epistatic interaction.


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