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IGF-1 rs35767 基因座多态性与肾功能长期下降的关系:一项日本回顾性纵向队列研究。

Association between polymorphism at IGF-1 rs35767 gene locus and long-term decline in renal function: a Japanese retrospective longitudinal cohort study.

机构信息

Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

Nephrology & Hypertension Research Unit, Miho Clinic, Tokyo, Japan.

出版信息

BMC Nephrol. 2021 Jun 2;22(1):207. doi: 10.1186/s12882-021-02408-9.

DOI:10.1186/s12882-021-02408-9
PMID:34078313
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8173978/
Abstract

BACKGROUND

Insulin-like growth factor-1 (IGF-1) acts on glucose and protein metabolism and human growth and also influences blood pressure and renal function. This study investigated whether the single-nucleotide polymorphism of IGF-1, rs35767, plays a role in metabolic syndrome indicators, including blood pressure, glucose metabolism, uric acid levels, and renal function.

METHODS

In this retrospective longitudinal cohort study, blood samples from 1506 Japanese individuals were collected and used for genotyping for variant rs35767: T > C in the IGF-1 upstream promoter. Data were analyzed to identify associations between IGF-1 genotypes and patient biochemical parameters, including the components of metabolic syndrome and the long-term change in renal function.

RESULTS

The cohort rs35767 genotypes included 650 CC carriers (43.2%), 687 TC carriers (45.6%), and 169 TT carriers (11.2%). Multiple regression analysis revealed no association between IGF-1 genotype and blood pressure, glycated hemoglobin level, and serum uric acid level. However, in females, blood pressure was negatively correlated with the TT genotype. Longitudinal observation revealed that the decline in eGFR over 10 years was greater in TT (- 18.51 ± 1.04 mL/min/1.73m) than in CC carriers (- 16.38 ± 0.52 mL/min/1.73m; P < 0.05).

CONCLUSION

The present study suggests that renal function declines faster in individuals with the TT genotype at the IGF-1 rs35767 locus than in those with the CC genotype, suggesting that the TT genotype is associated with the long-term chronological decline in renal function.

摘要

背景

胰岛素样生长因子-1(IGF-1)作用于葡萄糖和蛋白质代谢以及人体生长,还影响血压和肾功能。本研究旨在探讨 IGF-1 单核苷酸多态性 rs35767 是否与代谢综合征指标(包括血压、葡萄糖代谢、尿酸水平和肾功能)有关。

方法

本回顾性纵向队列研究共纳入 1506 名日本个体的血液样本,用于检测 IGF-1 上游启动子变异 rs35767:T>C 的基因型。分析数据以确定 IGF-1 基因型与患者生化参数(包括代谢综合征各组分和肾功能的长期变化)之间的关系。

结果

该队列 rs35767 基因型包括 650 名 CC 携带者(43.2%)、687 名 TC 携带者(45.6%)和 169 名 TT 携带者(11.2%)。多变量回归分析显示,IGF-1 基因型与血压、糖化血红蛋白水平和血清尿酸水平无关。然而,在女性中,血压与 TT 基因型呈负相关。纵向观察发现,在 10 年期间 eGFR 下降幅度在 TT 携带者中更大(-18.51±1.04 mL/min/1.73m),而在 CC 携带者中则较小(-16.38±0.52 mL/min/1.73m;P<0.05)。

结论

本研究表明,IGF-1 rs35767 位点 TT 基因型个体的肾功能下降速度快于 CC 基因型个体,提示 TT 基因型与肾功能的长期随时间下降有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4925/8173978/e300b1a2bd91/12882_2021_2408_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4925/8173978/6f10cf892ae5/12882_2021_2408_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4925/8173978/e300b1a2bd91/12882_2021_2408_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4925/8173978/6f10cf892ae5/12882_2021_2408_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4925/8173978/e300b1a2bd91/12882_2021_2408_Fig2_HTML.jpg

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Uric Acid and the Risks of Kidney Failure and Death in Individuals With CKD.尿酸与慢性肾脏病患者的肾衰竭和死亡风险。
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