Polymorphism of the cytokine genes and IgA nephropathy.
BACKGROUND
IgA nephropathy (IgAN) is a form of chronic glomerulonephritis of unknown etiology and pathogenesis. Cytokine gene polymorphisms regulate cytokine production and play a role in immune and inflammatory responses; these immunological responses thus are possibly involved in the etiology and pathogenesis of IgAN.


METHODS
We studied by polymerase chain reaction (PCR) polymorphisms of important cytokine genes of inflammation interleukin-1 (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 receptor antagonist (IL-1Ra) in 167 patients with IgAN and 400 healthy blood donor controls. IgAN patients had been followed up for 6 to 17 (median 11) years from renal biopsy.


RESULTS
Carriage of the IL-1beta allele 2 (IL1beta2) or IL-1Ra allele 2 (IL1RN*2) was associated with an increased risk of IgAN. These alleles were highly linked and the odds ratio (OR) of IgAN for carriage of both alleles was 1.8 (95% confidence interval 1.2 to 2.6; P = 0.002). Carriage of the TNF-alpha allele 2 (TNF2) was associated with a decreased risk of IgAN (OR 0.5, range 0.3 to 0.7; P = 0.001). The risk of IgAN was found to be highest in those carrying IL1beta2 and IL1RN*2 but not TNF2 as compared to those who did not carry both of these IL-1 cluster genes and were carriers of TNF2 (OR 5.0 (2.4-10.3); P < 0.001). None of the polymorphisms studied was associated with poor prognosis.


CONCLUSIONS
Carriage of IL1beta2 and IL1RN*2 together with non-carriage of TNF2 is associated with increased susceptibility, but not with a prognosis of IgAN.
Syrjänen
Jaana
J
Medical School, University Hospital, FIN-33014 University of Tampere, Tampere, Finland. jaana.syrjanen@uta.fi
Hurme
Mikko
M
Lehtimäki
Terho
T
Mustonen
Jukka
J
Pasternack
Amos
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D018450:Disease Progression; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D006417:Hematuria / Q000209:etiology; D006801:Humans; D006973:Hypertension / Q000209:etiology; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011507:Proteinuria / Q000209:etiology; D012795:Sialoglycoproteins / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha