Polymorphism of proinflammatory cytokine genes and albuminuria in the Japanese general population: the Takahata study
Polymorphism of proinflammatory cytokine genes and albuminuria in the Japanese general population: the Takahata study
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日本普通人群促炎细胞因子基因多态性和蛋白尿：高畑研究
DOI：
10.1093/ndt/gfr105
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Kubota I.
中科院分区：
文献类型：
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作者：
Mashima Y;Konta T;Kudo K;Suzuki K;Ikeda A;Ichikawa K;Shibata Y;Watanabe T;Tamiya G;Kato T;Kawata S;Kubota I.
背景：一系列促炎细胞因子在各种肾脏疾病的发生发展中起着重要作用，并且这些细胞因子的表达是经过基因修饰的。为探讨促炎细胞因子基因多态性与蛋白尿的关系，采用横断面研究方法，对2927例日本受试者白细胞介素1β、白细胞介素6、白细胞介素8、肿瘤坏死因子α、CC趋化因子配体1和单核细胞趋化蛋白1等6个促炎细胞因子基因进行单核苷酸多态性分析。结果：白蛋白尿(UACR≥30 mg/g)与IL-6基因rs2069852位A/A+A/G和CCL1基因rs228269位A/A显著相关(P=0.002)。调整传统危险因素后的多因素分析显示，这些基因型独立预测蛋白尿[IL-6中rs2069852处A/A+A/G基因型的优势比(OR)1.782，95%可信区间(CI)1.171~2.712，P=0.007；CCL1中rs228269处A/A基因型的OR 1.432，95%CI 1.128~1.770，P=0.003]。结论IL-6和CCL1基因的SNPs与白蛋白尿的发生有关，且这两种基因的联合作用对白蛋白尿的患病率和严重程度具有相加作用。这表明影响炎症反应的遗传因素可能影响日本普通人群肾脏损伤的发展。
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, includinginterleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, CC chemokine ligand 1 (CCL1)andmonocyte 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 theCCL1gene (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 inIL-6, and OR 1.432, 95% CI 1.128–1.770, P = 0.003 for the A/A genotype at rs228269 inCCL1]. 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 andCCL1genes 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.