Chinese women with 29–30 FMR1 CGG repeats have an earlier menopause

Abstract

Purpose: A strong, well-established non-linear relationship exists between fragile X mental retardation (FMR1) premutation and menopausal age. The aim of this study is to evaluate whether this relationship continues into the normal CGG repeat range.

Methods: FMR1 CGG repeats of 111 Chinese postmenopausal women from a prospective cohort and the relationship with age at menopause were analyzed. Associations of FMR1 genotypes with annually measured estradiol and follicle stimulating hormone (FSH) levels were also assessed.

Results: One premutation and two intermediate carriers were identified, with a prevalence of 0.90% and 1.80%, respectively. The age at menopause differed with statistical significance (p = 0.007) between women carrying bi-allelic 29–30 repeats (49.66 ± 3.26 years) and those carrying a different number of repeats (51.26 ± 2.74 years). Age at menopause among subgroups (≤28, 29–30, and ≥31 repeats) of alleles 1 and 2 were also different (p = 0.014, p = 0.044). FSH trajectories to final menstrual period differed between women with the bi-allelic 29–30 repeats and others (p = 0.019).

Conclusions: Women with 29–30 FMR1 CGG repeats may experience menopause approximately 2 years earlier than those carrying ≤28 or ≥31 CGG repeats, and have a longer FSH fluctuant period.

摘要

目的：脆性X智力低下（FMR1）的前突变与绝经年龄之间存在着一种强有力的、建立良好的非线性关系。本研究的目的是评估这种关系是否持续到正常的CGG重复范围内。

方法：对111例中国绝经后妇女的FMR1-CGG重复序列及其与绝经年龄的关系进行分析。此外, 还评估了FMR1基因型与每年测得的雌二醇和促卵泡激素（FSH）水平的相关性。

结果：发现1例前突变和2例中间携带者, 分别占0.90%和1.80%。携带两等位基因重复29-30次（49.66±3.26岁）和携带其他不同重复次数（51.26±2.74岁）的妇女绝经年龄差异有统计学意义（p=0.007）。等位基因1和2亚群（≤28、29-30和≥31重复）的更年期年龄也不同（p=0.014、p=0.044）。双等位基因重复29-30次的女性和其他女性的FSH到月经末期的轨迹不同（p=0.019）。

结论：FMR1-CGG重复29-30次的女性比那些FMR1-CGG重复≤28次或≥31次的女性更年期提前2年左右, FSH波动期更长。

Keywords:

• FMR1
• CGG repeats
• natural menopause
• menopausal age
• follicle stimulating hormone

Acknowledgements

The authors are deeply grateful to all participants involved in this study and to all of the doctors and researchers who participated in the study.

Potential conflict of interest

No potential conflict of interest was reported by the author(s).

Source of funding

This study was supported by the National Key Research and Development Program [grant number 2018YFC1002105]; CAMS Innovation Fund for Medical Sciences (CIFMS) [grant number 2017-I2M-1-002]; Wu Jieping Medical Foundation Clinical Research Project [grant number 320.6750.16183].