Three common variants of LEP, NPY1R and GPR54 show no association with age at menarche.
BACKGROUND
Twin and family studies indicate a significant heritability of pubertal timing and more specifically of age at menarche (AAM).


OBJECTIVE
Test the association of AAM with common variants of three candidate genes suspected to have a prominent role in reproductive physiology: leptin (LEP), neuropeptide Y receptor 1 (NPY1R) and GPR54.


METHODS
We selected the -2459 LEP, the rs7687423 NPY1R and thers350132 GPR54 variants as the more common coding or regulatory variants (minor allelic frequency >0.10) in these gene regions. To avoid stratification problems that can impair association studies, we used the Q-TDT method based on allele transmission to evaluate the relationship of these variants with AAM in 245 healthy women from 107 families of European ancestry.


RESULTS
We found no association of AAM with any of the studied variants.


CONCLUSIONS
Keeping in mind that common variants do not recapitulate the whole genetic variation in a given gene region, this study indicates that the studied LEP, NPY1R and GPR54 variants do not have a major influence upon pubertal timing in Caucasian women. Effects of these genetic loci on age at menarche can definitively be excluded only through determination of extended haplotypes in a larger cohort.
Rothenbuhler
Anya
A
Department of Pediatric Endocrinology and Institut National de la Santé et de la Recherche Médicale-U561, René Descartes Paris 5 University, Hôpital Saint-Vincent de Paul, Paris, France. anya.rothenbuhler@free.fr
Lotton
Chantal
C
Fradin
Delphine
D
D000293:Adolescent; D002648:Child; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D020738:Leptin / Q000235:genetics*; D008572:Menarche / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D000074502:Receptors, Kisspeptin-1; D017476:Receptors, Neuropeptide Y / Q000235:genetics*; D044465:White People / Q000235:genetics
C118688:KISS1R protein, human; D020738:Leptin; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D017476:Receptors, Neuropeptide Y