Genetic Variability of the Number of CAG Repeats in the X-Linked Androgen Receptor Gene and Human Embryonic Mortality

Distribution of the X-linked androgen receptor gene (AR) alleles with different number of CAG repeat units in the first exon was analyzed in spontaneous abortuses having the 46,XX karyotype. The increased frequency of alleles with low number of trinucleotide repeat units in these specimens compared to adult healthy women was revealed. For more detailed analysis, all AR alleles were grouped into three classes: A, with a low CAG repeat number (21 to 23); B, with a moderate repeat number (24 to 28); and C, with a high maximum repeat number (29 to 32). Statistically significant among-sample differences in the frequencies of AA genotypes, which prevailed in spontaneous abortuses, were revealed. The samples tested were also different by the mean squared distance between the AR allele lengths, which constituted 81.8 ± 0.4 and 53.2 ± 0.5 in healthy women and spontaneous abortuses, respectively. Based on the data on inverse correlation between the length of the CAG repeat sequence and transcriptional activity of the androgen receptor gene, a hypothesis on selection against female individuals with the small number of CAG repeats in the AR gene and high transcriptional activity of this locus in prenatal period of human ontogeny is advanced.