Gustin Stephanie L F, Ding Victoria Y, Desai Manisha, Leader Benjamin, Baker Valerie L
Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Stanford University School of Medicine, 900 Welch Road, Suite 20, Palo Alto, CA, 94034, USA.
Quantitative Sciences Unit, Center for Biomedical Informatics Research, Stanford University School of Medicine, 1070 Arastradero Road, Palo Alto, CA, 94304, USA.
J Assist Reprod Genet. 2015 Nov;32(11):1669-76. doi: 10.1007/s10815-015-0577-0. Epub 2015 Sep 26.
The objective of this analysis is to examine the relationship between Fragile X Mental Retardation 1 gene (FMR1) cytosine-guanine-guanine (CGG) repeat number and ovarian reserve, with a particular focus exclusively on the range of CGG repeat number below the premutation (PM) range (<55 CGG repeats).
Our study included female patients who underwent assessment of FMR1 CGG repeat number and serum anti-Mullerian hormone (AMH) in 2009-2014. To examine the association between FMR1 repeat number and serum AMH, we created three summary measures of CGG repeat number for the two alleles-"Sum," "Max," and "Gap" (absolute difference). Using multivariable regression models, controlling for age, we then analyzed the impact of these summary measures on AMH.
A total of 566 patients were included in our study. Using multivariable regression models, we found that the relationship between CGG repeat number and AMH differed depending on age. Specifically, in younger women, AMH increased by 7-8 % (Sum p < 0.01, Max p = 0.04) for every 1 unit increase in CGG repeat number. In contrast, starting at age 40, there was a 3 to 5 % decline in AMH for every 1 unit increase in CGG repeat number (Sum p < 0.01, Max p = 0.04).
This is the first study to report a statistically significant correlation of ovarian reserve and CGG repeat number in women with <55 CGG repeats. Although these women are generally considered to have a normal phenotype, our data suggest that increasing CGG repeat number within this normal range is associated with a more rapid decline in ovarian reserve.
本分析的目的是研究脆性X智力低下1基因（FMR1）胞嘧啶-鸟嘌呤-鸟嘌呤（CGG）重复次数与卵巢储备之间的关系，特别关注CGG重复次数在预突变（PM）范围以下（<55次CGG重复）的情况。
我们的研究纳入了2009年至2014年间接受FMR1 CGG重复次数和血清抗苗勒管激素（AMH）评估的女性患者。为了研究FMR1重复次数与血清AMH之间的关联，我们为两个等位基因创建了CGG重复次数的三个汇总指标——“总和”、“最大值”和“差距”（绝对差值）。然后，我们使用多变量回归模型，在控制年龄的情况下，分析这些汇总指标对AMH的影响。
我们的研究共纳入了566名患者。使用多变量回归模型，我们发现CGG重复次数与AMH之间的关系因年龄而异。具体而言，在年轻女性中，CGG重复次数每增加1个单位，AMH增加7%至8%（总和p<0.01，最大值p=0.04）。相比之下，从40岁开始，CGG重复次数每增加1个单位，AMH下降3%至5%（总和p<0.01，最大值p=0.04）。
这是第一项报告CGG重复次数<55次的女性中卵巢储备与CGG重复次数存在统计学显著相关性的研究。尽管这些女性通常被认为具有正常表型，但我们的数据表明，在这个正常范围内增加CGG重复次数与卵巢储备的更快下降有关。
