Page 221 - Biobehavioral Resilence to Stress

198 Biobehavioral Resilience to Stress

These publicly available databases gave us direct access to informa-

tion about genetic variations that reside in different parts of each gene and

also identify some properties of those variations that suggest physiological

importance. This information, which we summarize in Table 8.1, allows
the researcher to consider how many variations are located in transcription
factor (“trans fac”) binding sites and thus are likely to aff ect gene expres-
sion; how many variations are located in exon–intron boundaries and other

relevant positions that might influence gene splicing (“splice”) and thus
protein formation; and how many variations are located in coding regions
that create amino acid substitutions (“ns cSNPs”) and thus are likely to
influence protein structure.

Pharmacological Studies and the Exploitation
of Genetic Network Information

In the effort to identify genes that mediate a complex phenotype such as

PTSD, researchers can leverage existing pharmacologic knowledge about

biochemical pathways of known or putative relevance. This approach may
also provide additional insight into factors that influence response to specifi c

treatments. In fact, the field of pharmacogenetics itself is based on the notion
that it is possible to identify inherited DNA variations, which infl uence indi-
vidual responses to particular drugs or treatments (see also PharmGKB at
www.pharmgkb.org; Weber, 1997).
Table 8.2 presents a list of studies relevant to the administration of tyro-

sine, which has been shown to influence both animal and human responses
to stress, as well as cognitive and physiologic functional abilities in the face
of various types of stressors (Deijen, 2005).
Tyrosine is known to play a critical role in the biosynthesis and ulti-
mate release of catecholamines (Lieberman, 2003) and can be administered
to combat negative effects of stress (Banderet & Lieberman, 1989; Brady,

Brown & Thrumond, 1980; Dollins, Krock, Storm, Wurtman & Leiberman,

1995; Lieberman, et al., 1984; Lieberman, Georgelis, Maher & Yeghiayan,
2005; Magill et al., 2003; Schurleff , Thomas, Ahlers & Schrot, 1993; Shukitt-

Hale, Stillman & Leiberman, 1996; Shurleff , Thomas, Schrot, Kowalski &
Harford, 1994; Waters et al., 2003; Yeghiayan, Luo, Shukitt-Hale & Leiber-
man, 2001). The gene encoding tyrosine hydroxylase (TH) is involved in

tyrosine production. Therefore, variation in the TH gene might infl uence
the ability of the cell to generate and utilize tyrosine, which in turn might

also affect catecholamine production. Recently, Zhang et al. (2004) iden-

tified a number of naturally occurring variations in the TH gene, some
of which were shown to influence blood pressure and catecholaminergic

response to stress. It is of great interest then to determine whether TH gene

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