Associations between polymorphisms of interleukin-6 and related cytokine genes and serum liver damage markers: a cross-sectional study in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.
Associations between polymorphisms of interleukin-6 and related cytokine genes and serum liver damage markers: a cross-sectional study in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.
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DOI：
10.1016/j.gene.2014.12.025
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发表时间：
2015-02
期刊：
影响因子：
3.5
通讯作者：
Y. Sugimoto;K. Wakai;H. Nakagawa;S. Suma;Tae Sasakabe;Tatsuhiko Sakamoto;N. Takashima;Sadao Suzuki;S. Ogawa;K. Ohnaka;N. Kuriyama;K. Arisawa;H. Mikami;M. Kubo;S. Hosono;N. Hamajima;Hideo Tanaka
中科院分区：
文献类型：
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作者：
Y. Sugimoto;K. Wakai;H. Nakagawa;S. Suma;Tae Sasakabe;Tatsuhiko Sakamoto;N. Takashima;Sadao Suzuki;S. Ogawa;K. Ohnaka;N. Kuriyama;K. Arisawa;H. Mikami;M. Kubo;S. Hosono;N. Hamajima;Hideo Tanaka
包括白细胞介素-6（IL-6）在内的细胞因子在肝脏中发挥重要作用。本研究的目的是调查在一项大型日本队列研究的入组者中，细胞因子基因的潜在功能启动子的常见多态性与肝损伤标志物之间的关联。受试者包括3257名日本人（1608名男性和1649名女性，年龄35-69岁）。采用聚合酶链反应对5种细胞因子基因IL 1B（T-31 C）、IL 6（C-634 G）、IL 8（T-251 A）、IL 10（T-819 C）、肿瘤坏死因子-A（TNFA）（T-1031 C）和TNFA（C-857 T）启动子区的6个单核苷酸多态性（SNP）进行基因分型。通过自填问卷收集关于饮酒、吸烟习惯、身高和体重的信息。在常规健康检查中测定血清谷草转氨酶（AST）和丙氨酸转氨酶（ALT）。在6个SNPs基因分型中，IL 6多态性（rs 1800796，C-634 G）与肝损伤标志物AST的相关性最强。三种基因型之间的平均血清AST存在显著差异（平均值± SD，CC为22.7 ± 7.3 IU/L，CG为22.8 ± 7.7 IU/L，GG为24.3 ± 8.6 IU/L，方差分析p= 0.011）。通过一般线性模型校正潜在混杂因素后，差异仍显着。平均血清AST和ALT水平的变化尤其在男性中显著。因此，功能性多态性IL 6C-634 G可能通过不同的IL-6产生而影响血清AST和ALT水平。
Cytokines, including interleukin-6 (IL-6), play an important role in the liver. The aim of this study was to investigate associations between common polymorphisms in potential functional promoters of cytokine genes and liver damage markers among enrollees of a large Japanese cohort study. Subjects included 3257 Japanese individuals (1608 men and 1649 women, aged 35–69 years). Six single nucleotide polymorphisms (SNPs) in the promoter regions of five cytokine genes, IL1B (T-31C),IL6(C-634G),IL8(T-251A),IL10(T-819C), tumor necrosis factor-A (TNFA) (T-1031C), andTNFA(C-857T), were genotyped by polymerase chain reaction. Information regarding alcohol intake, smoking habits, height, and weight was collected by a self-administered questionnaire. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured during a routine health check-up. Of the six SNPs genotyped, anIL6polymorphism (rs1800796, C-634G) was most strongly associated with a liver damage marker, AST. Mean serum AST was significantly different among the three genotypes (mean ± SD, 22.7 ± 7.3 IU/L for CC, 22.8 ± 7.7 IU/L for CG, and 24.3 ± 8.6 IU/L for GG,p= 0.011 by analysis of variance). The differences remained significant after adjustment for potential confounders by general linear models. The variations in mean serum AST and ALT levels were marked especially among men. Thus, the functional polymorphismIL6C-634G may affect serum AST and ALT levels, possibly through different IL-6 production.