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GLP-1R 基因多态性与中国 2 型糖尿病患者血脂异常的关系:一项病例对照研究。

Association between GLP-1R gene polymorphism and dyslipidemia in Chinese patients with type 2 diabetes mellitus: A case-control study.

机构信息

Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong 6 Provincial Qianfoshan Hospital, Jinan, Shandong, China.

Jinan Xinhang Experimental Foreign Language School, Jinan, Shandong, China.

出版信息

Gene. 2023 Aug 20;878:147589. doi: 10.1016/j.gene.2023.147589. Epub 2023 Jun 24.

Abstract

OBJECTIVE

To evaluate the relationship between GLP-1R gene polymorphisms and type 2 diabetes mellitus with dyslipidemia and without dyslipidemia in China.

METHODS

A total of 200 patients with Type 2 Diabetes Mellitus (T2DM) were included in this study, including 115 with dyslipidemia and 85 without dyslipidemia. We used Sanger double deoxygenation terminal assay and PCR-RFLP to detect genotype of the GLP-1R rs10305420 and rs3765467 loci. T-test was used to analyze the association between gene polymorphisms and lipid indicators. SHEsis online analysis software was used to analyze the linkage balance effect of loci, and SPSS 26 was used to calculate the gene interaction by dominant model.

RESULTS

The genotype distribution of the two loci in the sample of this study was in accordance with Hardy-weinberg equilibrium. There were significant differences in the genotype distribution and allele frequency of rs3765467 between T2DM patients with and without dyslipidemia (GG 52.9%, GA + AA 47.1% vs. GG 69.6%, GA + AA 30.4%; P = 0.017). Under the dominant model, the effects of rs3765467 A allele and rs10305420 T allele on dyslipidemia had multiplicative interactions (P = 0.016) and additive interactions (RERI = 0.403, 95% CI [-2.708 to 3.514]; AP = 0.376, 95% CI [-2.041, 2.793]). Meanwhile, HbA levels in rs3765467 A allele carriers (GA + AA) were found to be significantly lower than those in patients with GG genotype (P = 0.006).

CONCLUSION

The rs3765467 (G/A) variant is associated with the incidence of dyslipidemia, and G allele may be a risk factor for dyslipidemia.

摘要

目的

评估 GLP-1R 基因多态性与中国 2 型糖尿病伴血脂异常和不伴血脂异常的关系。

方法

本研究纳入 200 例 2 型糖尿病(T2DM)患者,其中 115 例血脂异常,85 例血脂正常。采用 Sanger 双脱氧末端法和 PCR-RFLP 法检测 GLP-1R rs10305420 和 rs3765467 位点的基因型。采用 t 检验分析基因多态性与血脂指标的相关性。采用 SHEsis 在线分析软件分析位点的连锁平衡效应,采用 SPSS 26 计算显性模型的基因交互作用。

结果

本研究样本中两个位点的基因型分布符合 Hardy-Weinberg 平衡。T2DM 患者伴血脂异常与不伴血脂异常的 rs3765467 基因型分布和等位基因频率存在显著差异(GG 52.9%,GA+AA 47.1%比 GG 69.6%,GA+AA 30.4%;P=0.017)。在显性模型下,rs3765467 A 等位基因和 rs10305420 T 等位基因对血脂异常的影响具有相乘交互作用(P=0.016)和相加交互作用(RERI=0.403,95%CI[-2.708,3.514];AP=0.376,95%CI[-2.041,2.793])。同时,rs3765467 A 等位基因携带者(GA+AA)的 HbA 水平明显低于 GG 基因型患者(P=0.006)。

结论

rs3765467(G/A)变异与血脂异常的发生有关,G 等位基因可能是血脂异常的危险因素。

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