The effect of proinflammatory cytokine gene and angiotensin-converting enzyme polymorphisms on erythropoietin requirements in patients on continuous ambulatory peritoneal dialysis.
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.
Department of Renal Medicine and Transplantation, Royal London and St Bartholomew's Hospital, Whitechapel, London, United Kingdom. edsharps@doctors.org.uk
Edward J
EJ
Sharples
Mira
M
Varagunam
Paul J
PJ
Sinnott
Daniel J
DJ
McCloskey
Martin J
MJ
Raftery
Mohammad M
MM
Yaqoob
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010531:Peritoneal Dialysis, Continuous Ambulatory; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D011994:Recombinant Proteins
D016207:Cytokines; D011994:Recombinant Proteins; D004921:Erythropoietin; D004247:DNA; D007703:Peptidyl-Dipeptidase A