Polymorphism of proinflammatory cytokine genes and albuminuria in the Japanese general population: The Takahata study

Yusuke Mashima, Tsuneo Konta, Kosuke Kudo, Kazuko Suzuki, Ami Ikeda, Kazunobu Ichikawa, Yoko Shibata, Tetsu Watanabe, Gen Tamiya, Takeo Kato, Sumio Kawata, Isao Kubota

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background. A cluster of proinflammatory cytokines plays an important role in the development of various renal diseases, and the expression of these cytokines is genetically modified. To examine the association between polymorphisms of proinflammatory cytokine genes and albuminuria, a cross-sectional study was conducted in the general population. Methods. Single nucleotide polymorphisms (SNPs) in six proinflammatory cytokine genes, including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, CC chemokine ligand 1 (CCL1) and monocyte chemoattractant protein-1 (MCP-1), were genotyped in 2927 Japanese subjects. Urine albumin-creatinine ratio (UACR) was measured in morning spot urine samples. Results. Albuminuria (UACR ≥ 30 mg/g) was significantly associated with the A/A + A/G genotype at rs2069852 in the IL-6 gene (P = 0.01) and the A/A genotype at rs228269 in the CCL1 gene (P = 0.002). Multivariate analysis with adjustment for traditional risk factors showed that these genotypes independently predicted albuminuria [odds ratio (OR) 1.782, 95% confidence interval (CI) 1.171-2.712, P = 0.007 for the A/A + A/G genotype at rs2069852 in IL-6, and OR 1.432, 95% CI 1.128-1.770, P = 0.003 for the A/A genotype at rs228269 in CCL1]. The prevalence of albuminuria and the UACR were increased along with the increase of risk genotypes. Conclusions. This study revealed that SNPs in the IL-6 and CCL1 genes were associated with albuminuria, and the combination of these genotypes had an additive effect on the prevalence and severity of albuminuria. This indicates that genetic factors influencing inflammatory responses may affect the development of renal injury in the Japanese general population.

Original languageEnglish
Pages (from-to)3902-3907
Number of pages6
JournalNephrology Dialysis Transplantation
Volume26
Issue number12
DOIs
Publication statusPublished - 2011 Dec
Externally publishedYes

Fingerprint

Albuminuria
Chemokine CCL1
Genotype
Cytokines
Interleukin-6
Population
Genes
Urine
Albumins
Creatinine
Single Nucleotide Polymorphism
Odds Ratio
Confidence Intervals
Kidney
Chemokine CCL2
Interleukin-8
Interleukin-1
Multivariate Analysis
Tumor Necrosis Factor-alpha
Cross-Sectional Studies

Keywords

  • albuminuria
  • cytokine
  • general population
  • genotype
  • inflammation

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Polymorphism of proinflammatory cytokine genes and albuminuria in the Japanese general population : The Takahata study. / Mashima, Yusuke; Konta, Tsuneo; Kudo, Kosuke; Suzuki, Kazuko; Ikeda, Ami; Ichikawa, Kazunobu; Shibata, Yoko; Watanabe, Tetsu; Tamiya, Gen; Kato, Takeo; Kawata, Sumio; Kubota, Isao.

In: Nephrology Dialysis Transplantation, Vol. 26, No. 12, 12.2011, p. 3902-3907.

Research output: Contribution to journalArticle

Mashima, Y, Konta, T, Kudo, K, Suzuki, K, Ikeda, A, Ichikawa, K, Shibata, Y, Watanabe, T, Tamiya, G, Kato, T, Kawata, S & Kubota, I 2011, 'Polymorphism of proinflammatory cytokine genes and albuminuria in the Japanese general population: The Takahata study', Nephrology Dialysis Transplantation, vol. 26, no. 12, pp. 3902-3907. https://doi.org/10.1093/ndt/gfr105
Mashima, Yusuke ; Konta, Tsuneo ; Kudo, Kosuke ; Suzuki, Kazuko ; Ikeda, Ami ; Ichikawa, Kazunobu ; Shibata, Yoko ; Watanabe, Tetsu ; Tamiya, Gen ; Kato, Takeo ; Kawata, Sumio ; Kubota, Isao. / Polymorphism of proinflammatory cytokine genes and albuminuria in the Japanese general population : The Takahata study. In: Nephrology Dialysis Transplantation. 2011 ; Vol. 26, No. 12. pp. 3902-3907.
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AU - Mashima, Yusuke

AU - Konta, Tsuneo

AU - Kudo, Kosuke

AU - Suzuki, Kazuko

AU - Ikeda, Ami

AU - Ichikawa, Kazunobu

AU - Shibata, Yoko

AU - Watanabe, Tetsu

AU - Tamiya, Gen

AU - Kato, Takeo

AU - Kawata, Sumio

AU - Kubota, Isao

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N2 - Background. A cluster of proinflammatory cytokines plays an important role in the development of various renal diseases, and the expression of these cytokines is genetically modified. To examine the association between polymorphisms of proinflammatory cytokine genes and albuminuria, a cross-sectional study was conducted in the general population. Methods. Single nucleotide polymorphisms (SNPs) in six proinflammatory cytokine genes, including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, CC chemokine ligand 1 (CCL1) and monocyte chemoattractant protein-1 (MCP-1), were genotyped in 2927 Japanese subjects. Urine albumin-creatinine ratio (UACR) was measured in morning spot urine samples. Results. Albuminuria (UACR ≥ 30 mg/g) was significantly associated with the A/A + A/G genotype at rs2069852 in the IL-6 gene (P = 0.01) and the A/A genotype at rs228269 in the CCL1 gene (P = 0.002). Multivariate analysis with adjustment for traditional risk factors showed that these genotypes independently predicted albuminuria [odds ratio (OR) 1.782, 95% confidence interval (CI) 1.171-2.712, P = 0.007 for the A/A + A/G genotype at rs2069852 in IL-6, and OR 1.432, 95% CI 1.128-1.770, P = 0.003 for the A/A genotype at rs228269 in CCL1]. The prevalence of albuminuria and the UACR were increased along with the increase of risk genotypes. Conclusions. This study revealed that SNPs in the IL-6 and CCL1 genes were associated with albuminuria, and the combination of these genotypes had an additive effect on the prevalence and severity of albuminuria. This indicates that genetic factors influencing inflammatory responses may affect the development of renal injury in the Japanese general population.

AB - Background. A cluster of proinflammatory cytokines plays an important role in the development of various renal diseases, and the expression of these cytokines is genetically modified. To examine the association between polymorphisms of proinflammatory cytokine genes and albuminuria, a cross-sectional study was conducted in the general population. Methods. Single nucleotide polymorphisms (SNPs) in six proinflammatory cytokine genes, including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, CC chemokine ligand 1 (CCL1) and monocyte chemoattractant protein-1 (MCP-1), were genotyped in 2927 Japanese subjects. Urine albumin-creatinine ratio (UACR) was measured in morning spot urine samples. Results. Albuminuria (UACR ≥ 30 mg/g) was significantly associated with the A/A + A/G genotype at rs2069852 in the IL-6 gene (P = 0.01) and the A/A genotype at rs228269 in the CCL1 gene (P = 0.002). Multivariate analysis with adjustment for traditional risk factors showed that these genotypes independently predicted albuminuria [odds ratio (OR) 1.782, 95% confidence interval (CI) 1.171-2.712, P = 0.007 for the A/A + A/G genotype at rs2069852 in IL-6, and OR 1.432, 95% CI 1.128-1.770, P = 0.003 for the A/A genotype at rs228269 in CCL1]. The prevalence of albuminuria and the UACR were increased along with the increase of risk genotypes. Conclusions. This study revealed that SNPs in the IL-6 and CCL1 genes were associated with albuminuria, and the combination of these genotypes had an additive effect on the prevalence and severity of albuminuria. This indicates that genetic factors influencing inflammatory responses may affect the development of renal injury in the Japanese general population.

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