Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
J Clin Endocrinol Metab. 2018 Jan 1;103(1):228-234. doi: 10.1210/jc.2017-01860.
Recent genetic studies have identified genetic variants associated with age at pubertal onset. Whereas genome-wide association studies reported associations of several hundred genetic variants with timing of self-reported age at menarche, a recent clinical study focused on genetic variation affecting follicle-stimulating hormone action and clinically determined age at thelarche. The observations appear to be incongruent, as effect sizes varied substantially among the studies. Alternatively, this may point to a differential impact of specific genetic loci on distinct pubertal events.
To investigate whether top-candidate genetic variants exhibit a different impact on timing of thelarche vs menarche, respectively.
Cross-sectional and longitudinal study of healthy girls.
Population-based study in the Copenhagen area.
Girls (1478) were followed through puberty and genotyped for FSHB c.-211G>T (rs10835638), FSHR c.-29G>A (rs1394205), FSHR c.2039A>G (rs6116), LIN28B (rs7759938), INHA (rs4141153), MKRN3 (rs12148769), TMEM38B (rs10453225), and ZNF483 (rs10980921).
Clinical pubertal staging and anthropometric data.
We observed an association of LIN28B (rs7759938) with age at thelarche (P < 0.001, effect size: 0.27 year, 95% confidence interval: 0.12 to 0.42) and age at menarche (P = 0.005, 0.17 year, 0.05 to 0.29). FSHB c.-211G>T (rs10835638) and FSHR c.-29G>A (rs1394205) minor allele count was associated with age at thelarche (P = 0.004, 0.19 year, 0.06 to 0.31) but not with age at menarche (P = 0.97; all adjusted for body mass index z scores).
Our results indicate a differential impact of specific genetic loci on age at thelarche and menarche in healthy girls.
最近的遗传研究已经确定了与青春期开始年龄相关的遗传变异。全基因组关联研究报告了数百个遗传变异与自我报告的月经初潮年龄有关，而最近的一项临床研究则侧重于影响促卵泡激素作用和临床确定的初潮年龄的遗传变异。这些观察结果似乎不一致，因为研究之间的效应大小差异很大。或者，这可能表明特定遗传位点对不同的青春期事件有不同的影响。
研究顶级候选遗传变异是否对初潮和初潮的时间分别有不同的影响。
对健康女孩进行横断面和纵向研究。
哥本哈根地区的基于人群的研究。
对 1478 名女孩进行了随访，以了解青春期并对 FSHB c.-211G>T(rs10835638)、FSHR c.-29G>A(rs1394205)、FSHR c.2039A>G(rs6116)、LIN28B(rs7759938)、INHA(rs4141153)、MKRN3(rs12148769)、TMEM38B(rs10453225)和 ZNF483(rs10980921)进行基因分型。
临床青春期分期和人体测量数据。
我们观察到 LIN28B(rs7759938)与初潮年龄（P < 0.001，效应大小：0.27 岁，95%置信区间：0.12 至 0.42）和月经初潮年龄（P = 0.005，0.17 岁，0.05 至 0.29）相关。FSHB c.-211G>T(rs10835638)和 FSHR c.-29G>A(rs1394205)的次要等位基因计数与初潮年龄（P = 0.004，0.19 岁，0.06 至 0.31）相关，但与月经初潮年龄无关（P = 0.97；所有因素均调整为体质指数 z 分数）。
我们的研究结果表明，特定遗传位点对健康女孩的初潮和月经初潮年龄有不同的影响。
