Pro-/anti-inflammatory cytokine gene polymorphisms and chronic kidney disease: a cross-sectional study.
BACKGROUND
The aim of this study was to explore the associations between common potential functional promoter polymorphisms in pro-/anti-inflammatory cytokine genes and kidney function/chronic kidney disease (CKD) prevalence in a large Japanese population.


METHODS
A total of 3,323 subjects aged 35-69 were genotyped for all 10 single nucleotide polymorphisms (SNPs) in the promoter regions of candidate genes with minor allele frequencies of > 0.100 in Japanese populations. The estimated glomerular filtration rate (eGFR) and CKD prevalence (eGFR < 60 ml/min/1.73 m2) of the subjects were compared among the genotypes.


RESULTS
A higher eGFR and lower prevalence of CKD were observed for the homozygous variants of IL4 -33CC (high IL-4 [anti-inflammatory cytokine]-producing genotype) and IL6 -572GG (low IL-6 [pro-inflammatory cytokine]-producing genotype). Subjects with IL4 CC + IL6 GG showed the highest mean eGFR (79.1 ml/min/1.73 m2) and lowest CKD prevalence (0.0%), while subjects carrying IL4 TT + IL6 CC showed the lowest mean eGFR (73.4 ml/min/1.73 m2) and highest CKD prevalence (17.9%).


CONCLUSIONS
The functional promoter polymorphisms IL4 T-33C (rs2070874) and IL6 C-572G (rs1800796), which are the only SNPs that affect the IL-4 and IL-6 levels in Japanese subjects, were associated with kidney function and CKD prevalence in a large Japanese population.
Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan. rieokada@med.nagoya-u.ac.jp
Rieko
R
Okada
Kenji
K
Wakai
Mariko
M
Naito
Emi
E
Morita
Sayo
S
Kawai
Nobuyuki
N
Hamajima
Megumi
M
Hara
Naoyuki
N
Takashima
Sadao
S
Suzuki
Toshiro
T
Takezaki
Keizo
K
Ohnaka
Kokichi
K
Arisawa
Hiroshi
H
Hirohata
Keitaro
K
Matsuo
Haruo
H
Mikami
Michiaki
M
Kubo
Hideo
H
Tanaka
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000208:ethnology / Q000235:genetics / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
D016207:Cytokines