Journal Article

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 and Isao Kubota

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 26, issue 12, pages 3902-3907
Published in print December 2011 | ISSN: 0931-0509
Published online March 2011 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfr105
Polymorphism of proinflammatory cytokine genes and albuminuria in the Japanese general population: the Takahata study

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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.

Keywords: albuminuria; cytokine; general population; genotype; inflammation

Journal Article.  3567 words.  Illustrated.

Subjects: Nephrology

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