Brull, D.J., Montgomery, H.E., Sanders, J., Dhamrait, S., Luong, L., Rumley, A., Lowe, G.D.O. and Humphries, S.E. (2001) Interleukin-6 gene -174G gt C and -572G gt C promoter polymorphisms are strong predictors of plasma - Interleukin-6 levels after coronary artery bypass surgery. Arteriosclerosis, Thrombosis, and Vascular Biology, 21(9), pp. 1458-1463.
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Publisher's URL: http://atvb.ahajournals.org/cgi/content/full/21/9/1458
Abstract
Interleukin-6 (IL-6) synthesized in response to diverse stimuli may play an important role in bridging the inflammatory and atherosclerotic processes. The acute-phase response after coronary artery bypass graft surgery (CABG) is associated with the induction and release of cytokines, such as IL-6. We have examined the effect of common polymorphisms in the IL-6 gene promoter (-1746 gt C, -572G gt C, and -5976 gt A) on IL-6 levels after elective CABG. DNA extracted from the peripheral blood of 127 patients was amplified by polymerase chain reaction. IL-6 genotypes were resolved by gel electrophoresis after restriction enzyme digestion. Serum IL-6 was measured before surgery and in serial samples at 6, 24, 48, and 72 hours after CABG. Genotype distribution was as expected for a population in Hardy-Weinberg equilibrium for all polymorphisms. Rare allele frequencies (+/-95% CIs) were similar to those reported previously: -597A 0.36 (0.30 to 0.42), -572C 0.07 (0.04 to 0.10), and -1740 0.37 (0.31 to 0.43). The -1746 gt C and -5976 gt A genotypes were in strong allelic association (Delta =0.97, P lt 0.001). Baseline IL-6 levels did not significantly differ between patients with different genotypes for any polymorphism. However, 6 hours after CABG, peak IL-6 levels were significantly higher (P=0.03) in carriers of the -572C allele than in those of the -572GG genotype (355 +/- 67 versus 216 +/- 13 pg/mL, respectively) and in those with genotype -174CC compared with -174G allele carriers (287 +/- 31 versus 227 +/- 15 pg/mL, respectively; P=0.04). These effects remained statistically significant after adjusting for possible confounders, including age, sex, smoking, duration of cardiopulmonary bypass, aortic cross-clamp time, and total duration of surgery. These data demonstrate that IL-6 promoter polymorphisms influence peak IL-6 production after CABG, suggesting that these polymorphisms, which are functional in vitro, are also functional in vivo, suggesting a genetic influence on IL-6 levels after acute severe injury.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Lowe, Professor Gordon |
| Authors: | Brull, D.J., Montgomery, H.E., Sanders, J., Dhamrait, S., Luong, L., Rumley, A., Lowe, G.D.O., and Humphries, S.E. |
| Subjects: | R Medicine > RC Internal medicine |
| College/School: | College of Medical Veterinary and Life Sciences |
| Journal Name: | Arteriosclerosis, Thrombosis, and Vascular Biology |
| Publisher: | American Heart Association |
| ISSN: | 1079-5642 |
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