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HNF1A基因变异和单倍型与代谢综合征的关联:突尼斯人群的病例对照研究及荟萃分析

Association of HNF1A gene variants and haplotypes with metabolic syndrome: a case-control study in the Tunisian population and a meta-analysis.

作者信息

Dallali Hamza, Hechmi Meriem, Morjane Imane, Elouej Sahar, Jmel Haifa, Ben Halima Yosra, Abid Abdelmajid, Bahlous Afef, Barakat Abdelhamid, Jamoussi Henda, Abdelhak Sonia, Kefi Rym

机构信息

Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur in Tunis, BP 74, 13 Place Pasteur, Belvedere, 1002, Tunis, Tunisia.

University of Carthage, National Institute of Applied Science and Technology, Tunis, Tunisia.

出版信息

Diabetol Metab Syndr. 2022 Feb 2;14(1):25. doi: 10.1186/s13098-022-00794-0.

Abstract

BACKGROUND

Variants in the Hepatocyte Nuclear Factor 1 Alpha gene (HNF1A) are associated with lipoproteins levels and type 2 diabetes. In this study, we aimed to assess the association of HNF1A gene and haplotypes with the metabolic syndrome (MetS) and its components through an association study in the Tunisian population as well as by a meta-analysis.

METHODS

A total of 594 Tunisian individuals were genotyped for three variants (rs1169288, rs2464196 and rs735396) located in HNF1A gene using KASPar technology. Statistical analyses were performed with R software. The association was furthermore evaluated through a meta-analysis of our results with those obtained in a Moroccan population.

RESULTS

Our results showed no association between HNF1A variants and MetS in the Tunisian population. However, a significant association was observed between the variant rs735396 and a higher waist circumference. The stratified analysis according to the sex highlighted a significant association between the variant rs1169288 and high cholesterol levels only in women. Similarly, Haplotype analysis showed an association between the HNF1A minor haplotype and high total cholesterol mainly in women. Finally, our meta-analysis showed no association between HNF1A variants and MetS.

CONCLUSIONS

Our findings exclude the involvement of the three HNF1A variants rs1169288, rs2464196 and rs735396 in the susceptibility to MetS in our studied Tunisian population but emphasize the role of these variants in the cholesterol homeostasis with sex-specific differences, which may serve to rise clinical consideration to early statin therapy in women carrying these genetic variants.

摘要

背景

肝细胞核因子1α基因(HNF1A)的变异与脂蛋白水平及2型糖尿病相关。在本研究中,我们旨在通过对突尼斯人群的关联研究以及荟萃分析,评估HNF1A基因和单倍型与代谢综合征(MetS)及其组分之间的关联。

方法

使用KASPar技术对594名突尼斯个体的HNF1A基因中的三个变异(rs1169288、rs2464196和rs735396)进行基因分型。使用R软件进行统计分析。此外,通过将我们的结果与摩洛哥人群中获得的结果进行荟萃分析来评估这种关联。

结果

我们的结果显示,在突尼斯人群中,HNF1A变异与MetS之间无关联。然而,观察到变异rs735396与较高的腰围之间存在显著关联。按性别进行的分层分析突出显示,仅在女性中变异rs1169288与高胆固醇水平之间存在显著关联。同样,单倍型分析显示,HNF1A次要单倍型与高总胆固醇之间的关联主要在女性中存在。最后,我们的荟萃分析显示HNF1A变异与MetS之间无关联。

结论

我们的研究结果排除了rs1169288、rs2464196和rs735396这三个HNF1A变异参与我们所研究的突尼斯人群中MetS易感性的可能性,但强调了这些变异在胆固醇稳态中的作用,且存在性别特异性差异。这可能有助于提高对携带这些基因变异的女性早期他汀类药物治疗的临床关注度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/995c/8812021/69370d67510b/13098_2022_794_Fig1_HTML.jpg

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