The second to fourth digit ratio and variation in the androgen receptor gene

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Abstract

The second to fourth digit ratio (2D:4D) is sexually dimorphic, with lower mean values in males compared to females. It has been suggested that the sex difference in 2D:4D is determined prenatally, 2D:4D is negatively related to prenatal testosterone and positively to prenatal oestrogen, and that 2D:4D is a marker for levels of sex steroids during brain organisation. There is growing evidence that many sex-dependent behaviours are correlated with 2D:4D. However, there is no direct evidence for an effect of prenatal sex steroids on the digit ratio. The response to prenatal testosterone is dependent on the amount produced and the foetal sensitivity to the hormone. Variation in the X-linked androgen receptor gene (AR) determines sensitivity to testosterone. Alleles of AR with low numbers of CAG triplets respond to testosterone with high transactivational activity, while high numbers of CAG's are associated with increased insensitivity to testosterone. We show in a sample of 50 men (49 Caucasian subjects, 1 Caucasian/Chinese subject) that 2D:4D is a phenotypic correlate of AR structure. Right-hand 2D:4D was positively correlated with CAG number and individuals with low 2D:4D in their right hand compared to left hand had AR alleles with low CAG numbers. We discuss the implications of our findings for our understanding of the aetiology of 2D:4D, its relationships with sex-dependent behaviours, and the evolutionary implications of variation in 2D:4D and AR.

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Methods

In this preliminary study, we chose to restrict our sample to men. The AR is an X-linked gene. Males have one copy of the gene and females have two. Therefore, in males, we can be sure which AR is activated, in females we cannot. Our participants were 50 men (49 Caucasian participants and 1 subject of Caucasian/Chinese origin), with a mean age of 32.63±14.17 years, recruited from a Liverpool running club, a tennis club, and students and staff of Liverpool University. The study was approved by

Results

We found high and significant intraclass correlation coefficients (r1) between our first and second measures of 2D:4D (right-hand r1=.96, F=51.3, P=.0001; left-hand r1=.96, F=45.46, P=.0001). These values of r1 are not unusually high for 2D:4D ratios measured directly from the fingers (Manning, 2002). We concluded that our measures of 2D:4D reflected real differences between subjects.

The mean 2D:4D of the right hand was 0.977±0.04 and that of the left hand was 0.964±0.03. Similar male means

Discussion

We have found significant positive associations between CAG number of the AR, an inverse measure of sensitivity to testosterone, and right-hand 2D:4D and Dr-l. These relationships were in the expected direction and indicate that low right-hand 2D:4D and low Dr-l are associated with high sensitivity to testosterone. The sexual dimorphism in 2D:4D is determined early so an AR/2D:4D association suggests that the finger ratio is a correlate of sensitivity to prenatal testosterone. The relationships

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