The Cannabinoid Receptor 2 Q63R Variant Modulates the Relationship between Childhood Obesity and Age at Menarche

• Published in: PloS one 2015-10, Vol.10 (10), p.e0140142-e0140142
• Main Authors: Bellini, Giulia, Grandone, Anna, Torella, Marco, Miraglia del Giudice, Emanuele, Nobili, Bruno, Perrone, Laura, Maione, Sabatino, Rossi, Francesca
• Format: Article
• Language: English
• Subjects: Adolescent; Age; Age of Onset; Alleles; Apoptosis; Autoimmune diseases; Body mass; Body Mass Index; Cannabinoid CB2 receptors; Cannabinoids; Child; Childhood; Childhood obesity; Children; Children & youth; Chronology; Demographic aspects; Estrogens; Female; Folliculogenesis; Gene Frequency; Genetic aspects; Genetic Association Studies; Genetic Predisposition to Disease; Girls; Health aspects; Humans; Kinases; Menarche; Mutation, Missense; Obesity; Obesity - genetics; Obesity - physiopathology; Ovulation; Patients; Polymorphism; Polymorphism, Single Nucleotide; Proteins; Receptor, Cannabinoid, CB2 - genetics; Regression analysis; Single nucleotide polymorphisms; Surgery; Variance analysis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0140142

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. In this study, we investigated the role of the CB2 receptor in determining the age at menarche in obese girls. 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. 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