Interleukin-1 gene cluster polymorphisms are associated with nutritional status and inflammation in patients with end-stage renal disease.
BACKGROUND
Wasting and inflammation are two common risk factors for death in patients with end-stage renal disease (ESRD). Interleukin-1beta (IL-1beta) and its receptor antagonist (IL-1Ra) may play a pivotal role in the pathogenesis of wasting and inflammation.


METHODS
To investigate effects of the IL-1 gene cluster polymorphisms on wasting and inflammation, we studied 189 ESRD patients (52+/- 12 years, 62% males) close to the start of renal replacement therapy. 205 healthy volunteers served as controls. We analyzed the IL-1B -511C/T, -31C/T, and +3954C/T polymorphisms as well as a variable number of a tandem repeat (VNTR) in IL-1RN. Nutritional parameters included serum albumin level, subjective global nutritional assessment (SGA), and body composition evaluated by dual-energy X-ray absorptiometry (DXA). We used serum high-sensitivity C-reactive protein (hsCRP) as a marker of inflammation.


RESULTS
Wasting (SGA>1) was present in 31%, whereas inflammation (CRP>/=10 mg/l) was present in 36% of the patients. The male carriers of the -511T/T and -31C/C genotypes had a lower prevalence of wasting (p<0.05), higher body mass index (BMI) (p<0.05), and higher lean body mass (LBM) (p<0.01). In a stepwise multiple regression model, age (p<0.05), BMI (p<0.01) and the IL-1B -511 genotype (p<0.01) were independently associated with LBM. The carriers of the +3954T allele had a lower prevalence of inflammation (p<0.05) and lower serum hsCRP (p<0.05). The VNTR in IL-1RN was not associated with any markers.


CONCLUSIONS
The investigated IL-1 gene cluster polymorphisms were associated with nutritional status and inflammation in ESRD patients, but marked differences were found between the genders. These polymorphisms could have prognostic utility for predicting wasting and inflammation in ESRD patients.
Maruyama
Yukio
Y
Department of Clinical Science, Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden.
Nordfors
Louise
L
Stenvinkel
Peter
P
Heimburger
Olof
O
Bárány
Peter
P
Pecoits-Filho
Roberto
R
Axelsson
Jonas
J
Hoff
Catherine M
CM
Holmes
Clifford J
CJ
Schalling
Martin
M
Lindholm
Bengt
B
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000235:genetics*; D007375:Interleukin-1 / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D005810:Multigene Family; D009752:Nutritional Status / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017472:Receptors, Interleukin-1 / Q000235:genetics; D012307:Risk Factors; D012737:Sex Factors; D019282:Wasting Syndrome / Q000209:etiology / Q000235:genetics
D007375:Interleukin-1; D017472:Receptors, Interleukin-1