The Impact of “High-Producer” Interleukin-6 Haplotypes on Cardiovascular Morbidity and Mortality in a Kidney Transplant Population

Abstract Background At present, inflammation is considered to be one of the key players in the development and maintenance of atherosclerosis, with ample impact on renal transplant outcomes. Interleukin-6 (IL-6) levels and the underlying genetically determined “high-producer” status impact cardiovas...

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Bibliographic Details
Published in:Transplantation proceedings 2009-07, Vol.41 (6), p.2539-2543
Main Authors: Krüger, B, Walberer, A, Farkas, S, Tokmak, F, Obed, A, Schenker, P, Henning, B, Schlitt, H.J, Krämer, B.K, Banas, B
Format: Article
Language:English
Subjects:
Adult
Aged
Biological and medical sciences
Cardiovascular Diseases - epidemiology
Cardiovascular Diseases - genetics
Epidemiology
Female
Follow-Up Studies
Fundamental and applied biological sciences. Psychology
Fundamental immunology
General aspects
Graft Rejection - epidemiology
Graft Survival
Haplotypes
Histocompatibility Testing
HLA Antigens - genetics
Humans
Interleukin-6 - blood
Interleukin-6 - genetics
Kidney Function Tests
Kidney Transplantation - adverse effects
Kidney Transplantation - mortality
Kidney Transplantation - physiology
Male
Medical sciences
Middle Aged
Polymorphism, Single Nucleotide
Postoperative Complications - epidemiology
Public health. Hygiene
Public health. Hygiene-occupational medicine
Retrospective Studies
Surgery
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Time Factors
Tissue, organ and graft immunology
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Summary:Abstract Background At present, inflammation is considered to be one of the key players in the development and maintenance of atherosclerosis, with ample impact on renal transplant outcomes. Interleukin-6 (IL-6) levels and the underlying genetically determined “high-producer” status impact cardiovascular morbidity and mortality. In end-stage renal disease (ESRD) patients, the role of genetically determined IL-6 differences in cardiovascular and renal outcomes of kidney transplantation is controversial. In this study, we sought to clarify the influence of IL-6 haplotypes on cardiovascular and renal outcomes among kidney transplant recipients. Methods Three hundred fifty-two first kidney transplant patients were genotyped for the two “clade” IL-6 polymorphisms (−174 G/C and1888 G/T) and two missense polymorphisms (Pro32Ser, Asp162Val), which are known to influence IL-6 levels and outcome. Results We observed four IL-6 haplotypes among our population: CCAG: 57.0%, CCAT: 2.8%, GCAT: 39.2%, GCTT: 1.0%. After stratifying the haplotypes into diplotypes in three different models, we failed to observe associations with early or late graft outcomes, or with all-cause or cardiovascular mortality. These findings were also confirmed when we separately analyzed each polymorphism. Conclusion Despite evidence of associations in other transplant and ESRD cohorts, we could not confirm any association between IL-6 haplotypes/diplotypes and cardiovascular or graft-related outcomes among our population at high risk for inflammatory diseases.
ISSN:0041-1345
1873-2623
DOI:10.1016/j.transproceed.2009.06.123