Key result
Anxiety is linked to higher IL-6 levels only in adults with the IL-6R CC genotype.
Why the study?
Anxiety is linked to cardiovascular disease risk via inflammatory pathways, but whether inflammatory single-nucleotide polymorphisms moderate the relationship between anxiety and systemic inflammation was unknown.
Do single-nucleotide polymorphisms in inflammatory genes (CRP rs1205, IL-6 rs1800797, IL-6R rs4129267) moderate the association between anxiety and systemic inflammation (serum hsCRP and IL-6) in adults at risk for cardiovascular disease?
Cross-Sectional (n=398)
Yes
Do single-nucleotide polymorphisms in inflammatory genes (CRP rs1205, IL-6 rs1800797, IL-6R rs4129267) moderate the association between anxiety and systemic inflammation (serum hsCRP and IL-6) in adults at risk for cardiovascular disease?
Answers are grounded in this paper and cite their sources.
Genetic variation in the IL-6 receptor gene (rs4129267 CC genotype) moderates the link between anxiety and elevated IL-6 levels, suggesting genotypic differences in inflammatory susceptibility to psychological stress among adults at risk for CVD.
BACKGROUND: Cardiovascular disease is a significant health problem in the United States, attributed to more than 30% of all deaths annually. Anxiety has been associated with cardiovascular disease risk and is thought to be associated with cardiovascular disease risk through inflammatory pathways. OBJECTIVE: The purposes of this study were to examine the relationship between anxiety and systemic inflammation in individuals at risk for cardiovascular disease and to determine if single-nucleotide polymorphisms (SNPs) associated with inflammation moderate this relationship. METHODS: A secondary analysis was conducted using baseline data from a study investigating the impact of genetics on response to a cardiovascular disease risk reduction intervention. Anxiety was measured using the Brief Symptom Inventory. Protein levels for C-reactive protein and interleukin-6 (IL-6) were measured in serum, and genomic DNA was assayed for SNPs in the C-reactive protein, IL-6, and IL-6R genes. Multiple linear regressions were performed to examine if anxiety predicted inflammation and if SNPs moderated associations. RESULTS: Participants (N = 398) were white, aged 51 ± 13 years, and 73% women. There was a significant interaction between rs4129267 genotype and anxiety (P = .010), with the association significant only for individuals with the CC genotype (b = 0.243, SE = 0.04, P < .001). No moderation effect existed for rs1205 or rs1800797. CONCLUSION: Anxiety was positively associated with IL-6 protein levels, but moderation analysis indicated that this was significant only for individuals with the rs4129267 CC genotype. This suggests that genotypic differences may exist in anxiety response, placing certain individuals at higher risk for inflammation and, subsequently, cardiovascular disease.
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Key et al. (2020) conducted a cross-sectional in Cardiovascular disease risk (n=398). Anxiety symptoms (Brief Symptom Inventory Anxiety subscale) moderated by IL-6R rs4129267 CC genotype vs. IL-6R rs4129267 CT or TT genotypes (and rs1205, rs1800797 variants) was evaluated on Serum Interleukin-6 (IL-6) protein levels (log-10 transformed) (b = 0.243, SE = 0.04 for rs4129267 CC genotype (interaction β = -0.235), p=<0.001 (interaction P = 0.010)). Anxiety was positively associated with serum IL-6 levels only in adults with the IL-6R rs4129267 CC genotype.
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