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Clinical |
Department of Renal Medicine and Transplantation,1 Royal London and St Bartholomew's Hospital; Tissue Typing Laboratory,2 Royal London Hospital, Whitechapel, London, United Kingdom
Correspondence to: E.J. Sharples, Department of Renal Medicine and Transplantation, Royal London Hospital, Whitechapel, London, E1 1BB, United Kingdom.edsharps{at}doctors.org.uk
Background: The correction of anemia by recombinant
human erythropoietin (rHuEPO) improves quality of life and prolongs life in
end-stage renal failure. rHuEPO requirements for an individual are determined
by a range of factors, including iron deficiency and inflammation. Single
nucleotide polymorphisms in the promoter sequence of several proinflammatory
cytokines have been shown, in different fields of medicine, to influence the
cytokine response to different stimuli, with effects on clinical
outcome. Methods: The angiotensin-converting enzyme (ACE)
insertion/deletion polymorphism and polymorphisms in the promoter regions of
the genes for tumor necrosis factor alpha (–308 A/G), interleukin-6
(–174 G/C), and interferon gamma were examined for their association
with rHuEPO requirements in 112 patients on continuous ambulatory peritoneal
dialysis (CAPD). Genomic DNA was extracted from peripheral blood leukocytes
and genotyping performed with ARMS-PCR methodology, with sequence-specific
primers. We examined rHuEPO requirements and C-reactive protein at baseline
and during a 6-month study period. Results: We found no significant effect of
proinflammatory cytokine polymorphisms on rHuEPO responsiveness. However,
throughout the study, we observed that there was a significantly higher rHuEPO
requirement in the II and ID ACE genotypes compared with the DD group, which
remained an independent association following multivariate analysis. Conclusions: ACE insertion/deletion polymorphism may
determine rHuEPO responsiveness in CAPD patients and should be considered in
relative rHuEPO resistance.
KEY WORDS: ACE polymorphism; erythropoietin; cytokine.
Received 29 October 2004; accepted 18 May 2005.
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