Elevated Plasma C-reactive protein in chronically distressed subjects who carry the A allele of the TNF-alpha -308 G/A polymorphism.
OBJECTIVE
Sustained psychological stress may result in a state operationalized as "vital exhaustion." Exhaustion predicted coronary artery disease (CAD) events whereby increased inflammatory activity might mediate this link. Moreover, there is an emerging importance of gene-environmental interactions in CAD. We investigated the effect of exhaustion severity on plasma levels of C-reactive protein (CRP) and whether exhaustion might regulate CRP levels via the -308G/A polymorphism of the tumor necrosis factor (TNF)-alpha gene.


METHODS
We assessed exhaustion in 275 industrial employees (mean age +/- SD, 41 +/- 9 years, 88% men) using the Maastricht Questionnaire. Subjects were stratified as per exhaustion severity: none (N = 80), moderate (N = 128), and severe (N = 67). The TNF-alpha polymorphism was determined by real-time polymerase chain reaction, and plasma CRP levels were measured by a high-sensitivity immunoassay.


RESULTS
There was a significant interaction between exhaustion and the TNF-alpha polymorphism, explaining 4.5% in the variance of plasma CRP values (F(5,271) = 2.47, p =.033); the result held after controlling for classic cardiovascular risk factors. Adjusted mean CRP levels across exhaustion strata in GA (N = 70) and AA (N = 3) carriers combined were 0.91 mg/l (none), 1.78 mg/l (moderate), and 2.61 mg/l (severe) as compared with 1.24 mg/l, 1.61 mg/l, and 1.36 mg/l for the GG wild-type (N = 202).


CONCLUSIONS
The findings suggest that the A allele of the TNF-alpha -308 G/A polymorphism may mediate inflammation with exhaustion in a dose-response relationship, while with the GG wild-type exhaustion severity seems unrelated to CRP levels. The finding provides a rationale for gene-environmental interactions by which psychosocial factors may promote atherosclerosis and CAD.
Jeanmonod
Pascal
P
Institute for Behavioral Sciences, Swiss Federal Institute of Technology, Zürich, Switzerland.
von Känel
Roland
R
Maly
Friedrich E
FE
Fischer
Joachim E
JE
D000328:Adult; D000483:Alleles; D002097:C-Reactive Protein / Q000032:analysis* / Q000235:genetics; D002908:Chronic Disease; D003327:Coronary Disease / Q000097:blood / Q000235:genetics; D005221:Fatigue / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics; D008297:Male; D009784:Occupational Diseases / Q000097:blood / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012720:Severity of Illness Index; D013315:Stress, Psychological / Q000097:blood* / Q000235:genetics; D011795:Surveys and Questionnaires; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics*
D005819:Genetic Markers; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein