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

Rieko Okada; Kenji Wakai; Mariko Naito; Emi Morita; Sayo Kawai; Nobuyuki Hamajima; Megumi Hara; Naoyuki Takashima; Sadao Suzuki; Toshiro Takezaki; Keizo Ohnaka; Kokichi Arisawa; Hiroshi Hirohata; Keitaro Matsuo; Haruo Mikami; Michiaki Kubo; Hideo Tanaka

doi:10.1186/1471-2369-13-222230215

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

Rieko Okada, Kenji Wakai, Mariko Naito, Emi Morita, Sayo Kawai, Nobuyuki Hamajima, Megumi Hara, Naoyuki Takashima, Sadao Suzuki, Toshiro Takezaki, Keizo Ohnaka, Kokichi Arisawa, Hiroshi Hirohata, Keitaro Matsuo, Haruo Mikami, Michiaki Kubo, Hideo Tanaka

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Abstract

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.

Original language	English
Article number	2
Journal	BMC Nephrology
Volume	13
Issue number	1
DOIs	https://doi.org/10.1186/1471-2369-13-222230215
Publication status	Published - 2012

All Science Journal Classification (ASJC) codes

Nephrology

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10.1186/1471-2369-13-222230215

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Okada, R., Wakai, K., Naito, M., Morita, E., Kawai, S., Hamajima, N., Hara, M., Takashima, N., Suzuki, S., Takezaki, T., Ohnaka, K., Arisawa, K., Hirohata, H., Matsuo, K., Mikami, H., Kubo, M., & Tanaka, H. (2012). Pro-/anti-inflammatory cytokine gene polymorphisms and chronic kidney disease: A cross-sectional study. BMC Nephrology, 13(1), Article 2. https://doi.org/10.1186/1471-2369-13-222230215

Okada, R, Wakai, K, Naito, M, Morita, E, Kawai, S, Hamajima, N, Hara, M, Takashima, N, Suzuki, S, Takezaki, T, Ohnaka, K, Arisawa, K, Hirohata, H, Matsuo, K, Mikami, H, Kubo, M & Tanaka, H 2012, 'Pro-/anti-inflammatory cytokine gene polymorphisms and chronic kidney disease: A cross-sectional study', BMC Nephrology, vol. 13, no. 1, 2. https://doi.org/10.1186/1471-2369-13-222230215

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title = "Pro-/anti-inflammatory cytokine gene polymorphisms and chronic kidney disease: A cross-sectional study",

abstract = "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.",

author = "Rieko Okada and Kenji Wakai and Mariko Naito and Emi Morita and Sayo Kawai and Nobuyuki Hamajima and Megumi Hara and Naoyuki Takashima and Sadao Suzuki and Toshiro Takezaki and Keizo Ohnaka and Kokichi Arisawa and Hiroshi Hirohata and Keitaro Matsuo and Haruo Mikami and Michiaki Kubo and Hideo Tanaka",

year = "2012",

doi = "10.1186/1471-2369-13-222230215",

language = "English",

volume = "13",

journal = "BMC Nephrology",

issn = "1471-2369",

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TY - JOUR

T1 - Pro-/anti-inflammatory cytokine gene polymorphisms and chronic kidney disease

T2 - A cross-sectional study

AU - Okada, Rieko

AU - Wakai, Kenji

AU - Naito, Mariko

AU - Morita, Emi

AU - Kawai, Sayo

AU - Hamajima, Nobuyuki

AU - Hara, Megumi

AU - Takashima, Naoyuki

AU - Suzuki, Sadao

AU - Takezaki, Toshiro

AU - Ohnaka, Keizo

AU - Arisawa, Kokichi

AU - Hirohata, Hiroshi

AU - Matsuo, Keitaro

AU - Mikami, Haruo

AU - Kubo, Michiaki

AU - Tanaka, Hideo

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

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DO - 10.1186/1471-2369-13-222230215

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AN - SCOPUS:84855491053

SN - 1471-2369

VL - 13

JO - BMC Nephrology

JF - BMC Nephrology

IS - 1

M1 - 2

ER -

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

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