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在图基因组研究中,SNP-420/-358 处的抵抗素 G-A 单倍型与潜在的瘦素型肥胖指数相关。

Resistin G-A haplotype at SNP-420/-358 is associated with the latent sarcopenic obesity index in the toon genome study.

机构信息

Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan.

Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.

出版信息

J Diabetes Investig. 2023 May;14(5):686-694. doi: 10.1111/jdi.13998. Epub 2023 Mar 10.

Abstract

AIM/INTRODUCTION: Resistin, which induces insulin resistance, is mainly expressed in monocytes/macrophages in humans. We reported previously that serum resistin was highest in the G-A haplotype defined by resistin single nucleotide polymorphisms (SNPs) at -420 (rs1862513) and - 358 (rs3219175). As sarcopenic obesity is associated with insulin resistance, we aimed to examine whether serum resistin and its haplotypes were associated with sarcopenic obesity at a latent stage.

MATERIALS AND METHODS

We cross-sectionally analyzed 567 community-dwelling Japanese participants attending annual medical check-ups in which the sarcopenic obesity index was evaluated. The age- and gender-matched normal glucose tolerance subjects with G-A homozygotes and those with C-G homozygotes were examined via RNA-sequencing and pathway analysis (each n = 3), and RT-PCR (each n = 8).

RESULTS

In multivariate logistic regression analyses, the fourth quartile (Q4) of serum resistin and G-A homozygotes were both associated with the latent sarcopenic obesity index defined by a visceral fat area of ≥ 100 cm and grip strength Q1 after adjustment for age and gender, with or without other confounding factors. RNA sequencing and pathway analysis showed that tumor necrosis factor (TNF) was involved in the top five pathways in the whole blood cells of G-A homozygotes compared with C-G homozygotes. RT-PCR revealed that TNF mRNA was higher in G-A homozygotes than in C-G homozygotes.

CONCLUSIONS

The G-A haplotype was associated with the latent sarcopenic obesity index defined by grip strength in the Japanese cohort, could be mediated by TNF-α.

摘要

目的/引言:抵抗素主要在人类的单核细胞/巨噬细胞中表达,可诱导胰岛素抵抗。我们之前报道过,在抵抗素单核苷酸多态性(SNP)-420(rs1862513)和-358(rs3219175)定义的 G-A 单倍型中,血清抵抗素水平最高。由于肌少症性肥胖与胰岛素抵抗有关,我们旨在研究在潜在阶段,血清抵抗素及其单倍型是否与肌少症性肥胖有关。

材料和方法

我们对 567 名参加年度体检的社区居住的日本参与者进行了横断面分析,在这些参与者中评估了肌少症性肥胖指数。通过 RNA 测序和通路分析(每组 n=3)以及 RT-PCR(每组 n=8),对年龄和性别匹配的正常葡萄糖耐量受试者中 G-A 纯合子和 C-G 纯合子的空腹血清抵抗素和 G-A 纯合子进行了检查。

结果

在多变量逻辑回归分析中,血清抵抗素的四分位间距(Q4)和 G-A 纯合子均与年龄和性别调整后的潜在肌少症性肥胖指数相关,该指数由内脏脂肪面积≥100cm 和握力 Q1 定义,无论是否存在其他混杂因素。RNA 测序和通路分析显示,与 C-G 纯合子相比,G-A 纯合子的全血细胞中涉及前五个通路的 TNF 处于较高水平。RT-PCR 显示,G-A 纯合子的 TNF mRNA 水平高于 C-G 纯合子。

结论

在日本队列中,G-A 单倍型与握力定义的潜在肌少症性肥胖指数相关,可能由 TNF-α介导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf65/10119914/af3191fbfc0c/JDI-14-686-g003.jpg

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