The impact of "high-producer" interleukin-6 haplotypes on cardiovascular morbidity and mortality in a kidney transplant population.
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 and (1888)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.


CONCLUSIONS
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.
Krüger
B
B
Marienhospital Herne, Medizinische Klinik I, Klinikum der Ruhr-Universität Bochum, Herne, Germany. bernd.krueger@ruhr-uni-bochum.de
Walberer
A
A
Farkas
S
S
Tokmak
F
F
Obed
A
A
Schenker
P
P
Henning
B
B
Schlitt
H J
HJ
Krämer
B K
BK
Banas
B
B
D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology; D006085:Graft Survival; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000401:mortality / Q000502:physiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000453:epidemiology; D012189:Retrospective Studies; D013997:Time Factors
D006680:HLA Antigens; D015850:Interleukin-6