Variant in RGS2 moderates posttraumatic stress symptoms following potentially traumatic event exposure

https://doi.org/10.1016/j.janxdis.2008.12.005Get rights and content

Abstract

Polymorphisms in the RGS2 (regulator of G-protein signaling 2) gene were found to be associated with anxious behavior in mice and anxiety in humans. We examined whether rs4606, a single nucleotide polymorphism (SNP) of RGS2, and social support moderated risk for PTSD in an epidemiologic sample. The study examines 607 adults from the 2004 Florida Hurricanes study who returned buccal DNA samples via mail. rs4606 was associated with increased symptoms of posthurricane PTSD symptoms under conditions of high hurricane exposure and low social support (P < .05). Further, this polymorphism was associated with lifetime PTSD symptoms under conditions of lifetime exposure to a potentially traumatic event, and low social support (P < .001). These gene by environment interactions remained significant after adjustment for sex, ancestry, and age. RGS2 rs4606 modifies risk of postdisaster and lifetime PTSD symptoms under conditions of high stressor exposure. This is the first demonstration of gene–environment interaction for this locus.

Section snippets

Data collection and sample

This study examines data from 607 participants in the 2004 Florida Hurricanes Study who completed structured telephone interviews and provided saliva samples that yielded genotype data for the rs4606 polymorphism. Methodological details for the Florida Hurricanes Study are provided elsewhere (Acierno et al., 2007, Acierno et al., 2006; Galea et al., 2006, Kilpatrick et al., 2007). Demographic characteristics of the 607 sample participants were as follows: 64.9% women; 35.1% men; 22.6% ≤59 years

Results

Average number of posthurricane PTSD symptoms reported among those who provided valid genotype data for rs4606 in RGS2 (N = 607) was 1.62 (S.D. = 2.76), and the average number of lifetime PTSD symptoms reported was 3.16 (S.D. = 3.61). Thirty-seven percent of individuals (N = 224) endorsed low social support, and was associated with posthurricane and lifetime PTSD symptoms (r's = .24, .28, respectively, P's < .001). Similarly, stressor exposure was associated with PTSD symptom counts. High hurricane

Discussion

Our results demonstrate that rs4606, a polymorphism in the RGS2 gene, moderates the risk of PTSD symptom severity under high environmental stress conditions of low social support and high hurricane exposure (or PTE). To our knowledge, this is the first study to date that examines RGS2 through a G × E model in a population-based human sample in relation to PTSD. Consistent with Leygraf et al. (2006) but (in terms of the identity of the associated allele) not with Smoller et al. (2008), the ‘C’

Conflict of interest

The authors declare no conflicting financial or other competing interests.

Acknowledgments

This research was supported by NIMH grant MH05220 (principal investigator: Ron Acierno, Ph.D.). Dr. Amstadter is supported by US-NIMH 083469. Dr. Koenen is supported by NIMH grants K08-MH070627 and MH078928.

References (42)

  • A. Caspi et al.

    Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene

    Science

    (2003)
  • H. Cui et al.

    Association of RGS2 gene polymorphisms with suicide and increased RGS2 immunoreactivity in the postmortem brain of suicide victims

    Neuropsychopharmacology

    (2007)
  • D. Falush et al.

    Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies

    Genetics

    (2003)
  • J.R. Freedy et al.

    Understanding acute psychological distress following natural disaster

    Journal of Traumatic Stress

    (1994)
  • S. Galea et al.

    Social context and the psychobiology of posttraumatic stress

    Annals of the New York Academy of Sciences

    (2006)
  • S. Galea et al.

    Psychological sequelae of the September 11 terrorist attacks in New York city

    New England Journal of Medicine

    (2002)
  • S. Galea et al.

    The epidemiology of post-traumatic stress disorder after disasters

    Epidemiology Review

    (2005)
  • I.I. Gottesman et al.

    The endophenotype concept in psychiatry: etymology and strategic intentions

    American Journal of Psychiatry

    (2003)
  • S.P. Heximer et al.

    Hypertension and prolonged vasoconstrictor signaling in RGS2-deficient mice

    Journal of Clinical Investigation

    (2003)
  • S. Hollinger et al.

    Cellular regulation of RGS proteins: modulators and integrators of G protein signaling

    Pharmacology Review

    (2002)
  • M.W. Hollmann et al.

    Receptors, G proteins, and their interactions

    Anestesiology

    (2005)
  • Cited by (91)

    • Genetics of Stress Responsiveness

      2020, Stress: Genetics, Epigenetics and Genomics Volume 4: Handbook of Stress
    View all citing articles on Scopus
    View full text