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  • One of the critical functions of the product of the

    2021-01-13

    One of the critical functions of the product of the AR gene is to activate the expression of target genes. This transactivation activity resides in the N-terminal domain of the protein encoded in exon 1, which contains polymorphic repeats. These trinucleotide repeats, (CAG) and (GGC), encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. The length of CAG repeat sequence is inversely correlated with transcriptional activity of the androgen receptor (Kittles et al., 2001). The number of CAG repeats in normal persons ranges from 17 to 29. The increase in CAG trinucleotide repeats up to 40 has been implicated in spinal and bulbar muscular atrophy (Kennedy disease) (La Spada, Wilson, Lubahn, Harding, & Fischbeck, 1991). Shorter CAG repeat length appears to be correlated with AR deactivation that could be associated to higher risk of prostate cancer, younger age of diagnosis and poor response to endocrine therapy (Debes & Tindall, 2002). The second trinucleotide repeat (GGC), which encodes a polyglycine tract, (Gln), is less well studied than the polyglutamine tract polymorphism and there is no direct functional association between polyglycine tract length and receptor activity. Two studies have examined associations of AR gene polymorphisms with personality traits. Jönsson et al. (2001) looked at the CAG repeat polymorphism in relation to scores on the Karolinska Scales of Personality in a convenience sample of Swedish adults. They found significant univariate associations of shorter repeats with traits related to 73122 receptor and aggression, but these were non-significant after correction for multiple statistical testing. They concluded that replication attempts would be worthwhile. Comings, Muhleman, Johnson, and MacMurray (2002) investigated the association of the GGC repeat polymorphism with personality measures in a sample of US patients and out-patient volunteers. They found that the 16-repeat allele was associated with the Assaultiveness scale of the Buss–Durkee Hostility Inventory, the Impulsivity scale of the Temperament and Character Inventory, the Acting Out scale of the Defense Style Questionnaire and internal Locus of Control. The AR GGC repeat polymorphism has also been examined for association with psychiatric disorders. Comings, Chen, Wu, and Muhleman (1999) looked at attention-deficit/hyperactivity disorder, conduct disorder and oppositional defiant disorder in patients with Tourette’s syndrome and controls. They found lower risk for these disorders to be associated with a haplotype which combined long alleles of both the CAG and GGC repeat polymorphisms. These authors also cited unpublished data showing lower novelty seeking scores in substance abusers with this haplotype. Although none of the above studies looked specifically at P, the behavioural characteristics associated with AR polymorphisms in these studies are generally typical of high P individuals. In the present study we report data from a community sample of adults who were assessed for P, E and N. They were genotyped for the DBH C-1021T polymorphism, which has been shown to account for variation in plasma DβH levels (Zabetian et al., 2001), and also for both the CAG and GGC repeat polymorphisms of the AR gene which have been associated with P-like behavioural characteristics in a number of studies. These DBH and AR polymorphisms were predicted to be associated with P specifically. The sample was also given the Behavioural Inhibition System/Behavioural Activation System (BIS/BAS) scales (Carver & White, 1994) which are designed to measure Gray’s (1987) dimensions of personality. We have previously reported that BIS is correlated with N and BAS with E (Jorm et al., 1999). We did not predict that the DBH and AR polymorphisms would be associated with the BIS/BAS scales, but report the results for completeness.
    Method The survey procedure has been described previously (Jorm et al., 1998) and is only briefly reiterated here.