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

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

Hamza Dallali  1 , Meriem Hechmi  1   2 , Imane Morjane  3 , Sahar Elouej  1 , Haifa Jmel  1 , Yosra Ben Halima  1 , Abdelmajid Abid  1   4 , Afef Bahlous  5 , Abdelhamid Barakat  3 , Henda Jamoussi  1   4 , Sonia Abdelhak  1   6 , Rym Kefi  7   8
Affiliations

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

Hamza Dallali et al. Diabetol Metab Syndr. .

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.

Keywords: Haplotype; Hepatocyte Nuclear Factor-1-Alpha gene; Lipids; Metabolic disorders; North Africa; SNP.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Linkage disequilibrium (LD) plot for the three genotyped HNF1A polymorphisms in the Tunisian study sample. Each number in the squares refers to the r2 coefficient of LD between the correspondent SNPs multiplied by 100. The LD plot was generated using the Haploview software (version 4.2)
Fig. 2
Fig. 2
Forest plots showing the meta-analysis results of the association between rs1169288 (A > C) and MetS in women. a Genetic model: AC vs AA, b Genetic model: CC vs AA, c Genetic model: AC + CC vs AA, d Genetic model: CC vs AA + AC. The forest plots were generated using “rmeta” R library
See this image and copyright information in PMC

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