Lack of association between the ESR1 rs9340799 polymorphism and age at menarche: a meta-analysis

It has been reported that the estrogen receptor alpha (ESR1) rs9340799 polymorphism is associated with age at menarche (AAM). However, recent investigations have generated inconsistent results. This study aimed to establish a more precise estimation of the association between this polymorphism and AAM. A meta-analysis was conducted based on an in silico literature search using PubMed. Six studies presenting continuous data, including ESR1 rs9340799 genotype frequencies, were selected. Effect size was estimated using Hedges' adjusted g with 95% confidence intervals (CIs), which were calculated based on the standardized mean difference between groups of subjects and different genotypes. No evidence of an association between the ESR1 rs9340799 polymorphism and AAM was found in the pooled continuous data under any genotype comparison (AA vs GG+AG: Hedges' g = -0.085, 95%CI = -0.202-0.032, P = 0.156; GG vs AA+AG: Hedges' g = 0.143, 95%CI = -0.041-0.327, P = 0.129; A vs G: Hedges' g = 0.187, 95% CI = -0.032-0.406, P = 0.095). Moreover, a funnel plot generated using this data was found to be symmetrical using the Egger (P = 0.797) and Begg tests (P = 0.851), indicating the absence of publication bias. In summary, our meta-analysis shows that the ESR1 rs9340799 polymorphism is not a significant, independent contributing factor to AAM. To validate this finding, further studies involving larger numbers of participants are needed.