Tsinopoulou Vasiliki Rengina, Bacopoulou Flora, Fidani Styliani, Christoforidis Athanasios
2nd Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, University General Hospital AHEPA, Stilponos Kyriakidi 1, Thessaloniki, 54636, Greece.
Center for Adolescent Medicine and UNESCO Chair in Adolescent Health Care, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Aghia Sophia Children's Hospital, Athens, Greece.
Hormones (Athens). 2025 Mar;24(1):167-177. doi: 10.1007/s42000-024-00594-3. Epub 2024 Sep 4.
Menarche, the first menstrual period marking the onset of female reproduction, is a milestone of female puberty. The timing of menarche determines the timing of later phases of pubertal maturation in girls and has major implications for health later in life, including behavioral and psychosocial disorders during adolescence and fertility problems and increased risk for certain diseases in adulthood. Over the last few decades, a continuous decline in age at menarche has been noted, with environmental factors contributing to this change in the timing of menarche. However, a genetic component of age at menarche and pubertal onset has been strongly suggested by studies in families and twins wherein up to approximately 80% of the variance in puberty onset can be explained by heritability. Gene association studies have revealed several genetic loci involved in age at menarche, among which LIN28B has emerged as a key regulator of female growth and puberty. LIN28B, a human homolog of Lin28 of C. elegans, is a known RNA-binding protein that regulates let-7 microRNA biogenesis. Genome-wide association studies have identified the association of polymorphisms in the LIN28B gene with age at menarche in several population cohorts worldwide. In this paper, we review the genetic factors contributing to age of menarche, with particular focus on the identified polymorphisms in LIN28B gene.
月经初潮是标志女性生殖开始的首次月经，是女性青春期的一个里程碑。月经初潮的时间决定了女孩青春期后期成熟阶段的时间，并对其日后的健康有重大影响，包括青春期的行为和心理社会障碍、生育问题以及成年后患某些疾病的风险增加。在过去几十年里，人们注意到月经初潮年龄持续下降，环境因素导致了月经初潮时间的这种变化。然而，家族和双胞胎研究有力地表明，月经初潮年龄和青春期开始存在遗传因素，其中高达约80%的青春期开始差异可由遗传力解释。基因关联研究已经揭示了几个与月经初潮年龄有关的基因位点，其中LIN28B已成为女性生长和青春期的关键调节因子。LIN28B是秀丽隐杆线虫Lin28的人类同源物，是一种已知的调节let-7微小RNA生物合成的RNA结合蛋白。全基因组关联研究已经在全球多个群体队列中确定了LIN28B基因多态性与月经初潮年龄的关联。在本文中，我们综述了影响月经初潮年龄的遗传因素，特别关注LIN28B基因中已确定的多态性。
