title: The Cannabinoid Receptor 2 Q63R Variant Modulates the Relationship between Childhood Obesity and Age at Menarche.
abstract: BACKGROUND
  The ovary is an important site where gene variants modulate pubertal timing. The cannabinoid receptor 2 (CB2) is expressed in the ovary, plays a role in folliculogenesis and ovulation, and can be modulated by estrogens. Obesity is strictly associated with early menarche and is characterized by sex hormone and endocannabinoid derangement.
  
  
  OBJECTIVE
  In this study, we investigated the role of the CB2 receptor in determining the age at menarche in obese girls.
  
  
  METHODS
  We studied a cohort of 240 obese girls (age 11.9±3 years; BMI z-score 2.8±0.8). The age at menarche (if it had already occurred) was recorded at the time of the visit or via phonecall. The CNR2 rs35761398 polymorphism, which leads to the CB2 Q63R variant, was detected by the TaqMan assay.
  
  
  RESULTS
  In total, 105 patients were homozygous for the R63-coding allele (RR), 113 were QR and 22 were QQ. Variance analysis revealed a significantly earlier age of menarche in subjects carrying the Q63 allele, which was also found after adjusting for BMI z-score (11±1.2 vs. 11.6±1.2 years, p = 0.0003). Logistic regression analysis demonstrated that patients homozygous for the Q allele had a 2.2-fold higher risk (odds ratio = 2.2; CI1.1-3.4; p = 0.02) of presenting with an early menarche (age at menarche <12 years).
  
  
  CONCLUSIONS
  We demonstrated for the first time the association between the CB2 Q63R functional variant and the age at menarche in a cohort of Italian obese girls.
authors.affiliation: Department of Experimental Medicine, Pharmacology Division, Second University of Naples, Naples, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Bellini
authors.affiliation: Department of Woman, Child and of General and Specialist Surgery, Second University of Naples, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Grandone
authors.affiliation: Department of Woman, Child and of General and Specialist Surgery, Second University of Naples, Naples, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Torella
authors.affiliation: Department of Woman, Child and of General and Specialist Surgery, Second University of Naples, Naples, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Miraglia del Giudice
authors.affiliation: Department of Woman, Child and of General and Specialist Surgery, Second University of Naples, Naples, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Nobili
authors.affiliation: Department of Woman, Child and of General and Specialist Surgery, Second University of Naples, Naples, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Perrone
authors.affiliation: Department of Experimental Medicine, Pharmacology Division, Second University of Naples, Naples, Italy.
authors.forename: Sabatino
authors.initials: S
authors.lastname: Maione
authors.affiliation: Department of Woman, Child and of General and Specialist Surgery, Second University of Naples, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rossi
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D015992:Body Mass Index; D002648:Child; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008572:Menarche; D020125:Mutation, Missense; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics*
chemical_list: C588309:CNR2 protein, human; D043885:Receptor, Cannabinoid, CB2