No Evidence that 2D:4D is Related to the Number of CAG Repeats in the Androgen Receptor Gene

Front Endocrinol (Lausanne). 2013 Dec 5:4:185. doi: 10.3389/fendo.2013.00185. eCollection 2013.

Abstract

The length ratio of the second to the fourth digit (2D:4D) is a putative marker of prenatal testosterone (T) effects. The number of CAG repeats (CAGn) in the AR gene is negatively correlated with T sensitivity in vitro. Results regarding the relationship between 2D:4D and CAGn are mixed but have featured prominently in arguments for and against the validity of 2D:4D. Here, I present random-effects meta-analyses on 14 relevant samples with altogether 1904 subjects. Results were homogeneous across studies. Even liberal estimates (upper limit of the 95% CI) were close to zero and therefore suggested no substantial relationship of CAGn with either right-hand 2D:4D, left-hand 2D:4D, or the difference between the two. However, closer analysis of the effects of CAGn on T dependent gene activation in vitro and of relationships between CAGn and T dependent phenotypic characteristics suggest that normal variability of CAGn has mostly no, very small, or inconsistent effects. Therefore, the lack of a clear association between CAGn and 2D:4D has no negative implications for the latter's validity as a marker of prenatal T effects.

Keywords: 2D:4D; AR gene; CAG repeats; meta-analysis; testosterone.