¹Tokyo Metropolitan Institute of Medical Science, Addictive Substance Project, Tokyo, Japan, ²Dept Neuropsychiatry, Hirosaki Univ Sch Med, Neuropsychiatry, Aomori, Japan

Background: It has been shown that the translocator protein 18 kDa (TSPO) located on the outer mitochondrial membrane is associated with a variety of cellular functions including steroidogenesis and inflammatory cell modulation. In our previous studies, the density of platelet TSPO was significantly correlated with trait anxiety rather than state anxiety in normal human subjects (Nakamura et al.,Psychopharmacology 162:301-303, 2002), which may reflect polymorphism of the TSPO gene (Nakamoto et al., Neurosci Abstr. 2006).

Aims & Objectives: In the present study, we have further examined the TSPO gene regarding gender and age for 164 normal human subjects (89 males, 75 females, age 20-60).

Method: Genomic DNA was prepared from lymphocytes , and the subjects were screened for sequence variations on the TSPO gene. We focused on the single nucleotide polymorphism at a position of 485 (485G>A), which was consisted of G/G (60.4%), G/A (32.3%) and A/A (7.3%).

Results: Binding assay for platelet TSPO densities revealed that no significant differences were observed among the means of G/G, G/A and A/A of either male or female subjects. However, there were significant differences among the variances of male, particularly with age, in the order of G/G > G/A > AA. Females with G/G, G/A, and possibly A/A, had significantly higher densities of TSPO with larger variances compared with the male counterparts (p<0.01 for G/G and G/A), suggesting that females are more sensitive to anxiety than males.

Discussion & Conclusions: We conclude that the G allele in the 485Ｇ＞A polymorphism of the human TSPO gene can be a risk factor for stress, in addition to gender and age differences.