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KLF14 基因型调节变异与心脏糖尿病患者发病机制的生化关联。

Biochemical association of regulatory variant of KLF14 genotype in the pathogenesis of cardiodiabetic patients.

机构信息

Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Saudi Arabia.

Health Sciences Research Unit, Jouf University, Sakaka, Al-Jouf, Saudi Arabia.

出版信息

Front Endocrinol (Lausanne). 2023 Jun 7;14:1176166. doi: 10.3389/fendo.2023.1176166. eCollection 2023.

DOI:10.3389/fendo.2023.1176166
PMID:37351102
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10282989/
Abstract

BACKGROUND AND PURPOSE

The study focuses on examining the relationship between a single nucleotide polymorphism (SNP) in KLF14 rs4731702 and risk of type 2 diabetes mellitus (T2DM) and dyslipidemia in different ethnic populations. The purpose of this study was to evaluate the association between KLF14 rs4731702 and serum lipid profile and to determine the frequency distribution of KLF14 rs4731702 among T2DM and cardiometabolic patients.

METHODS

A total of 300 volunteers were recruited, consisting of three groups: 100 healthy individuals, 100 individuals diagnosed with T2DM, and 100 individuals diagnosed with cardiometabolic disorders. Biochemical analysis of blood samples was conducted to assess various biomarkers related to glycemic control and lipid profile. This involved measuring levels of glucose, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and ApoA1. Genotyping analysis was performed to investigate KLF14 rs4731702 polymorphism. The Tetra ARMS-PCR method was employed for genotyping analysis.

RESULTS

The results of biochemical profiling revealed a significant association between altered glycemic biomarkers and lipid profile in diseased patients compared to healthy participants. The frequencies of KLF14 rs4731702 alleles and genotypes were compared between the control group and T2DM group. A statistically significant difference was observed, indicating a potential association between KLF14 rs4731702 and T2DM. In the dominant inheritance model of KLF14 rs4731702 SNP, a statistically significant difference [odds ratio (95% confidence interval)] of 0.56 (0.34 -0.96) was found between the control and T2DM subjects. This suggests that the presence of certain genotypes influences the risk of T2DM. In T2DM patients, individuals carrying the C allele exhibited compromised insulin sensitivity, decreased HDL-C and ApoA1 levels, and increased serum glucose, TG, and LDL-C concentrations. Conversely, TT genotype carriers demonstrated increased levels of HDL-C and ApoA1, lower insulin resistance, serum glucose, LDL-C, and TG levels.

CONCLUSION

The study's findings indicate that dyslipidemia in T2DM patients is associated with reduced KLF14 functionality due to CC and CT genotypes, leading to insulin resistance and an increased risk of cardiovascular diseases. Additionally, risk of KLF14 rs4731702 polymorphism was found to increase with age and was more prevalent in female than in male individuals. These insights contribute to understanding genetic factors influencing the development and progression of T2DM and dyslipidemia in different ethnic populations.

摘要

背景与目的

本研究旨在探讨 KLF14 rs4731702 单核苷酸多态性(SNP)与 2 型糖尿病(T2DM)和血脂异常在不同种族人群中的风险之间的关系。本研究的目的是评估 KLF14 rs4731702 与血清脂质谱的关系,并确定 KLF14 rs4731702 在 T2DM 和心脏代谢患者中的频率分布。

方法

共招募了 300 名志愿者,分为三组:100 名健康个体、100 名 T2DM 患者和 100 名心脏代谢障碍患者。对血液样本进行生化分析,以评估与血糖控制和脂质谱相关的各种生物标志物。这包括测量血糖、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和载脂蛋白 A1 的水平。进行 KLF14 rs4731702 多态性的基因分型分析。采用 Tetra ARMS-PCR 方法进行基因分型分析。

结果

生化特征分析结果显示,与健康参与者相比,患病患者的血糖生物标志物和脂质谱存在显著差异。比较对照组和 T2DM 组 KLF14 rs4731702 等位基因和基因型的频率。观察到统计学上的显著差异,表明 KLF14 rs4731702 与 T2DM 之间存在潜在关联。在 KLF14 rs4731702 SNP 的显性遗传模型中,对照组和 T2DM 组之间存在统计学显著差异[优势比(95%置信区间)]0.56(0.34-0.96)。这表明某些基因型会影响 T2DM 的风险。在 T2DM 患者中,携带 C 等位基因的个体表现出胰岛素敏感性降低、HDL-C 和载脂蛋白 A1 水平降低以及血清葡萄糖、TG 和 LDL-C 浓度升高。相反,TT 基因型携带者表现出 HDL-C 和载脂蛋白 A1 水平升高、胰岛素抵抗降低、血清葡萄糖、LDL-C 和 TG 水平降低。

结论

本研究结果表明,T2DM 患者的血脂异常与 CC 和 CT 基因型导致的 KLF14 功能降低有关,从而导致胰岛素抵抗和心血管疾病风险增加。此外,发现 KLF14 rs4731702 多态性的风险随着年龄的增长而增加,且女性比男性更为普遍。这些发现有助于了解影响不同种族人群中 T2DM 和血脂异常发生和发展的遗传因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06e/10282989/8fa11a8ca04f/fendo-14-1176166-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06e/10282989/189c3acf81a0/fendo-14-1176166-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06e/10282989/8fa11a8ca04f/fendo-14-1176166-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06e/10282989/189c3acf81a0/fendo-14-1176166-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06e/10282989/8fa11a8ca04f/fendo-14-1176166-g002.jpg

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