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Negative Affectivity and Inflammation: Moderation by the Glucocorticoid Receptor-9beta Polymorphism

Lim, Alvin (2014) Negative Affectivity and Inflammation: Moderation by the Glucocorticoid Receptor-9beta Polymorphism. Master's Thesis, University of Pittsburgh. (Unpublished)

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Growing evidence suggests that negative emotions may play a role in the upregulation of innate inflammatory processes and associated disease risk. Although the hypothalamic-adrenal-pituitary (HPA) axis is believed to play a role in these associations, empirical evidence is mixed. Inconsistencies may reflect individual differences in glucocorticoid receptor (GR) sensitivity, the capacity of immune cells to respond to anti-inflammatory effects of GC-mediated signaling. We examined whether genotypes of a single nucleotide polymorphism (SNP) in the GR gene—GR-9beta (rs6198), the minor (G) allele of which confers reduced GR sensitivity—moderated associations of negative affectivity (NA) and inflammatory activity. Subjects were middle-aged men and women of European ancestry participating in two phases of the Adult Health and Behavior Project (51% F; 30-54yr). NA was assessed by the neuroticism subscale of the NEO Personality Inventory and by the Positive and Negative Affect Schedule. In a subset of participants in the second phase of the AHAB project (AHAB-2) (51% F; 30-54yr), peripheral inflammation was additionally assessed by in vitro stimulated production of IL-6, interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-8 (IL-8), while NA was also assessed by ecological momentary assessment. In bivariate and hierarchical regression analyses adjusted for potential covariates, none of the NA measures predicted any of the inflammatory cytokine levels. However, subjects homozygous for the GR-9β G allele had higher IL-6 levels than those of alternate genotypes after adjustment for age, gender, and years of school (β = .057, p = .045, R2 = .047). Although GR-9β genotype was not associated with any of the stimulated cytokines, the interaction of GR-9β was significant, and showed that greater PANAS NA scores associated with greater IL-1β levels, but only among G allele homozygotes (β = .127, p = .027, ∆R2 = .015). While these results raise the possibility that GR-9β G allele homozygotes show increased inflammatory susceptibility to negative emotionality, this pattern was not retained in analyses of circulating IL-6, or stimulated production of IL-6, TNF-α, and IL-8. We found limited evidence that genotypes of the GR-9β polymorphism moderated associations of NA and measures of peripheral inflammation.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Lim, Alvinall105@pitt.eduALL105
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMarsland, Anna L.marsland@pitt.eduMARSLAND
Committee MemberManuck, Stephen B.manuck@pitt.eduMANUCK
Committee MemberBovbjerg, Dana H.bovbjergdh@upmc.eduDHB15
Date: 22 May 2014
Date Type: Publication
Defense Date: 30 August 2013
Approval Date: 22 May 2014
Submission Date: 16 April 2014
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 74
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Psychology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: inflammation, negative affect, GR-9β, rs6198
Date Deposited: 22 May 2014 19:45
Last Modified: 19 Dec 2016 14:41


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