Open Access Research article

Pro-/anti-inflammatory cytokine gene polymorphisms and chronic kidney disease: a cross-sectional study

Rieko Okada1*, Kenji Wakai1, Mariko Naito1, Emi Morita1, Sayo Kawai1, Nobuyuki Hamajima1, Megumi Hara2, Naoyuki Takashima3, Sadao Suzuki4, Toshiro Takezaki5, Keizo Ohnaka6, Kokichi Arisawa7, Hiroshi Hirohata8, Keitaro Matsuo9, Haruo Mikami10, Michiaki Kubo11, Hideo Tanaka9 and The Japan Multi-Institutional Collaborative Cohort (J-MICC)Study Group

Author Affiliations

1 Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan

2 Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan

3 Department of Health Science, Shiga University of Medical Science, Otsu, Japan

4 Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

5 Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan

6 Department of Geriatric Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan

7 Department of Preventive Medicine, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan

8 Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan

9 Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan

10 Division of Cancer Registry, Prevention and Epidemiology, Chiba Cancer Center, Chiba, Japan

11 Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, Yokohama, Japan

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BMC Nephrology 2012, 13:2  doi:10.1186/1471-2369-13-2

Published: 9 January 2012



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.


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.


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%).


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.