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

Transplant Proc. 2009 Jul-Aug;41(6):2539-43. doi: 10.1016/j.transproceed.2009.06.123.

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 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.

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.

MeSH terms

  • Adult
  • Aged
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / genetics
  • Female
  • Follow-Up Studies
  • Graft Rejection / epidemiology
  • Graft Survival
  • HLA Antigens / genetics
  • Haplotypes
  • Histocompatibility Testing
  • Humans
  • Interleukin-6 / blood
  • Interleukin-6 / genetics*
  • Kidney Function Tests
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / mortality
  • Kidney Transplantation / physiology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Postoperative Complications / epidemiology
  • Retrospective Studies
  • Time Factors

Substances

  • HLA Antigens
  • Interleukin-6