CYP19A1 variation in healthy children: associations with breast development and pubertal gynecomastia.

IF 3.4 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Endocrine Connections Pub Date : 2026-09-01 DOI:10.1530/EC-26-0182

Veronica L R Groendahl, Stine A Holmboe, Alexander S Busch, Casper P Hagen, Jørgen H Petersen, Trine H Johannsen, Kristian Almstrup, Hanne Frederiksen, Anders Juul, Lise Aksglaede

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Abstract

Background: CYP19A1 encodes aromatase, the enzyme converting androgens to estrogens, thereby influencing breast tissue development in healthy children.

Objective: To examine associations between CYP19A1 single nucleotide polymorphisms (SNPs) and circulating estradiol (E2) and testosterone (T), the E2/T ratio and age at thelarche in girls, and the presence of gynecomastia in boys.

Methods: A total of 1,023 healthy participants (aged 5.9-20.0 years) from the Copenhagen Puberty Study were assessed for pubertal status, and serum sex steroid concentrations were measured by LC-MS/MS. Genotyping of CYP19A1 SNPs (rs727479 A>C, rs2899472 A>C and rs10046 C>T) was performed.

Results: Girls with the AA genotype in rs727479 and rs2899472 showed tendencies toward earlier pubertal onset. In a combined efficacy allele model, each additional allele was associated with 1.6 months earlier puberty (P = 0.06), and girls with 5-6 vs 0-2 efficacy alleles presented with significantly lower pubertal age (P = 0.02). The CYP19A1 genotype was not associated with E2, T or E2/T levels. Boys with the CC genotype in rs727479 had the highest prevalence of pubertal gynecomastia (73%, P < 0.01). Boys with gynecomastia showed higher E2 and T (SDS) than unaffected boys (both P < 0.01), with no difference in E2/T. In age-matched analyses, E2 (SDS) remained elevated in boys with gynecomastia (0.81 vs 0.19, P = 0.04).

Conclusion: CYP19A1 variants may influence pubertal timing in girls. In boys, pubertal gynecomastia appeared to be linked with the CYP19A1 genotype and was associated with elevated E2 concentrations.

Significance statement: Aromatase, encoded by CYP19A1, catalyzes the conversion of androgens to estrogens. The contribution of common CYP19A1 genetic variants to variation in pubertal development in healthy children is not fully understood. In this cohort from the Copenhagen Puberty Study, we examined associations between CYP19A1 polymorphisms and circulating sex steroid concentrations, age at puberty and pubertal gynecomastia in boys. By integrating genetic, hormonal and clinical pubertal data, this study provides additional insights into potential links between aromatase-related genetic variation and normal pubertal development.

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健康儿童CYP19A1变异：与乳房发育和青春期男性乳房发育的关系

背景：CYP19A1编码芳香化酶，一种将雄激素转化为雌激素的酶，从而影响健康儿童乳腺组织的发育。目的：探讨CYP19A1单核苷酸多态性（snp）与循环雌二醇（E2）、睾酮(T)、E2/T比值、女孩起始年龄和男孩男性乳房发育之间的关系。方法：对来自哥本哈根青春期研究的1023名健康参与者（年龄5.9-20.0岁）进行青春期状态评估，并采用LC-MS/MS法测定血清性类固醇浓度。对CYP19A1 snp （rs727479 A>C, rs2899472 A>C, rs10046 C>T）进行基因分型。结果：携带rs727479和rs2899472 AA基因型的女孩青春期发育倾向较早。在疗效-等位基因联合模型中，每增加一个等位基因，青春期提前1.6个月（p = 0.06），拥有5-6个疗效等位基因的女孩比拥有0-2个疗效等位基因的女孩青春期年龄明显降低（p = 0.02）。CYP19A1基因型与E2、T或E2/T水平无关。rs727479 CC基因型男孩青春期男性乳房发育率最高（73%,p < 0.01）。男性乳房发育症男孩E2和T （SDS）高于正常男孩（p均< 0.01），E2/T无显著差异。在年龄匹配分析中，E2 （SDS）在男性乳房发育症男孩中仍然升高（0.81比0.19,p = 0.04）。结论：CYP19A1变异可能影响女孩青春期发育时间。在男孩中，青春期男性乳房发育似乎与CYP19A1基因型有关，并与E2浓度升高有关。意义声明：芳香酶由CYP19A1编码，催化雄激素向雌激素的转化。常见的CYP19A1基因变异对健康儿童青春期发育的影响尚不完全清楚。在哥本哈根青春期研究的队列中，我们研究了CYP19A1多态性、循环性类固醇浓度、青春期年龄和男孩青春期男性乳房发育之间的关系。通过整合基因、激素和临床青春期数据，本研究为芳香酶相关基因变异与正常青春期发育之间的潜在联系提供了额外的见解。

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来源期刊

Endocrine Connections Medicine-Internal Medicine

CiteScore

5.00

自引率

3.40%

发文量

361

审稿时长

6 weeks

期刊介绍： Endocrine Connections publishes original quality research and reviews in all areas of endocrinology, including papers that deal with non-classical tissues as source or targets of hormones and endocrine papers that have relevance to endocrine-related and intersecting disciplines and the wider biomedical community.