Bellini Giulia, Grandone Anna, Torella Marco, Miraglia del Giudice Emanuele, Nobili Bruno, Perrone Laura, Maione Sabatino, Rossi Francesca
Department of Experimental Medicine, Pharmacology Division, Second University of Naples, Naples, Italy.
Department of Woman, Child and of General and Specialist Surgery, Second University of Naples, Naples, Italy.
PLoS One. 2015 Oct 8;10(10):e0140142. doi: 10.1371/journal.pone.0140142. eCollection 2015.
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 <12 years).
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.
卵巢是基因变异调节青春期启动时间的重要部位。大麻素受体2（CB2）在卵巢中表达，在卵泡发生和排卵中起作用，且可受雌激素调节。肥胖与初潮过早密切相关，其特征为性激素和内源性大麻素紊乱。
在本研究中，我们调查了CB2受体在肥胖女孩初潮年龄决定中的作用。
我们研究了一组240名肥胖女孩（年龄11.9±3岁；BMI z评分2.8±0.8）。初潮年龄（如果已经发生）在就诊时或通过电话记录。通过TaqMan分析检测导致CB2 Q63R变异的CNR2 rs35761398多态性。
总共105例患者为编码R63等位基因的纯合子（RR），113例为QR，22例为QQ。方差分析显示，携带Q63等位基因的受试者初潮年龄显著更早，在调整BMI z评分后也发现了这一情况（11±1.2岁对11.6±1.2岁，p = 0.0003）。逻辑回归分析表明，Q等位基因纯合的患者初潮过早（初潮年龄<12岁）的风险高2.2倍（优势比 = 2.2；CI1.1 - 3.4；p = 0.02）。
我们首次在一组意大利肥胖女孩中证明了CB2 Q63R功能变异与初潮年龄之间的关联。
