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

Dallali, Hamza; Hechmi, Meriem; Morjane, Imane; Elouej, Sahar; Jmel, Haifa; Halima, Yosra Ben; Abid, A.; Bahlous, Afef; Barakat, Abdelhamid; Jamoussi, H.; Abdelhak, Sonia; Kéfi, Rym

doi:10.1186/s13098-022-00794-0

Cited by 4 publications

(2 citation statements)

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“…The C allele of the HNF1A rs735396 polymorphism was previously associated with the components of metabolic syndrome in the Tunisian population [ 63 ], as well as altered CRP levels [ 35 , 36 , 41 ], whereas the T allele was associated with the development of pancreatic cancer [ 46 ]. In our study, no significant differences were detected in the distribution of the HNF1A rs735396 genotypes and alleles between the PTSD and control groups; however, this SNP was found to be indicative of increased inflammation based on the observed associations with plasma N-glycome in patients with PTSD.…”

Section: Discussionmentioning

confidence: 99%

Genetic and Epigenetic Association of Hepatocyte Nuclear Factor-1α with Glycosylation in Post-Traumatic Stress Disorder

Tudor

Konjevod

Erjavec

et al. 2022

Genes

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Post-traumatic stress disorder (PTSD) is a complex trauma-related disorder, the etiology and underlying molecular mechanisms of which are still unclear and probably involve different (epi)genetic and environmental factors. Protein N-glycosylation is a common post-translational modification that has been associated with several pathophysiological states, including inflammation and PTSD. Hepatocyte nuclear factor-1α (HNF1A) is a transcriptional regulator of many genes involved in the inflammatory processes, and it has been identified as master regulator of plasma protein glycosylation. The aim of this study was to determine the association between N-glycan levels in plasma and immunoglobulin G, methylation at four CpG positions in the HNF1A gene, HNF1A antisense RNA 1 (HNF1A-AS1), rs7953249 and HNF1A rs735396 polymorphisms in a total of 555 PTSD and control subjects. We found significant association of rs7953249 and rs735396 polymorphisms, as well as HNF1A gene methylation at the CpG3 site, with highly branched, galactosylated and sialyated plasma N-glycans, mostly in patients with PTSD. HNF1A-AS1 rs7953249 polymorphism was also associated with PTSD; however, none of the polymorphisms were associated with HNF1A gene methylation. These results indicate a possible regulatory role of the investigated HNF1A polymorphisms with respect to the abundance of complex plasma N-glycans previously associated with proinflammatory response, which could contribute to the clinical manifestation of PTSD and its comorbidities.

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Section: Discussionmentioning

confidence: 99%

Genetic and Epigenetic Association of Hepatocyte Nuclear Factor-1α with Glycosylation in Post-Traumatic Stress Disorder

Tudor

Konjevod

Erjavec

et al. 2022

Genes

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“…It is characterized by a rich genetic background due to the admixture between Berber (early settlers in North Africa) and Eurasiatic and Sub-Saharan components ( Kefi et al, 2015 ). Like a mosaic, the North African genetic background represents a valuable and unique source for genetic investigations ( Ben Halima et al, 2017 ; Jmel et al, 2018 ; Arauna et al, 2019 ; Romdhane et al, 2021 ; Dallali et al, 2022 ) and the implementation of precision medicine.…”

Section: Introductionmentioning

confidence: 99%

Decoding the genetic relationship between Alzheimer’s disease and type 2 diabetes: potential risk variants and future direction for North Africa

Boukhalfa,

Jmel,

Kheriji

et al. 2023

Front. Aging Neurosci.

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IntroductionAlzheimer’s disease (AD) and Type 2 diabetes (T2D) are both age-associated diseases. Identification of shared genes could help develop early diagnosis and preventive strategies. Although genetic background plays a crucial role in these diseases, we noticed an underrepresentation tendency of North African populations in omics studies.Materials and methodsFirst, we conducted a comprehensive review of genes and pathways shared between T2D and AD through PubMed. Then, the function of the identified genes and variants was investigated using annotation tools including PolyPhen2, RegulomeDB, and miRdSNP. Pathways enrichment analyses were performed with g:Profiler and EnrichmentMap. Next, we analyzed variant distributions in 16 worldwide populations using PLINK2, R, and STRUCTURE software. Finally, we performed an inter-ethnic comparison based on the minor allele frequency of T2D-AD common variants.ResultsA total of 59 eligible papers were included in our study. We found 231 variants and 363 genes shared between T2D and AD. Variant annotation revealed six single nucleotide polymorphisms (SNP) with a high pathogenic score, three SNPs with regulatory effects on the brain, and six SNPs with potential effects on miRNA-binding sites. The miRNAs affected were implicated in T2D, insulin signaling pathways, and AD. Moreover, replicated genes were significantly enriched in pathways related to plasma protein binding, positive regulation of amyloid fibril deposition, microglia activation, and cholesterol metabolism. Multidimensional screening performed based on the 363 shared genes showed that main North African populations are clustered together and are divergent from other worldwide populations. Interestingly, our results showed that 49 SNP associated with T2D and AD were present in North African populations. Among them, 11 variants located in DNM3, CFH, PPARG, ROHA, AGER, CLU, BDNF1, CST9, and PLCG1 genes display significant differences in risk allele frequencies between North African and other populations.ConclusionOur study highlighted the complexity and the unique molecular architecture of North African populations regarding T2D-AD shared genes. In conclusion, we emphasize the importance of T2D-AD shared genes and ethnicity-specific investigation studies for a better understanding of the link behind these diseases and to develop accurate diagnoses using personalized genetic biomarkers.

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Genetic Polymorphisms Associated with Metabolic Syndrome in North Africa: Systematic Review and Meta-Analysis

Farhane,

Motrane,

Anaibar

et al. 2023

Biomed. Pharmacol. J.

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Background: Metabolic syndrome (MetS) is a multifactorial disorder characterized by the aggregation of various metabolic disorders, including obesity, hyperglycemia, hypertriglyceridemia, hypoHDLemia and hypertension. In addition to environmental influences, genetic factors can play a major role in the development of MetS. Objective: The present bibliographic review aims to examine the contribution of candidate gene polymorphisms to MetS susceptibility in North African populations. Methods: A systematic review search was conducted to identify pertinent articles published on Embase, PubMed, and Web of Science from their inception to August 2, 2023 to obtain all reported genetic data related to MetS in North African populations. Results: According to the literature search strategy, 785 articles were initially obtained from the cited databases, and 15 more papers were found utilizing other sources. Following the filtering procedure, 25 papers totalising 3925 cases and 4431 controls were included, from which only 13 were eligible for meta-analysis. The meta-analysis results suggest that the genetic cumulative risk of developing MetS was substantially influenced by four polymorphisms, including APOA5 (rs3135506 and rs662799), APOC3 (rs5128), and FTO (rs9939609), while the vaspin polymorphism (rs2236242) was reported to play a protective role from MetS. Furthermore, no significant association was observed between rs1169288, rs2464196, and rs735396 polymorphisms at HNF1A gene and MetS development. A narrative synthesis of association studies revealed that a multitude of candidate genes is associated with MetS components. In all included studies, 14 polymorphisms were linked to obesity, and 13 polymorphisms were associated with hyperglycemia. The association of hypertension with polymorphisms represents the lowest number, with only seven polymorphisms associated with this MetS component. In the other hand, studies about MetS in North Africa considering the genetic association of candidate genes with dyslipidemia component represents the highest number with 20 polymorphisms in approximately 14 genes. Conclusion: The present meta-analysis suggests that four polymorphisms, namely rs3135506 and rs662799 at APOA5 gene, rs5128 at APOC3 and rs9939609 at FTO, contributed significantly to the MetS risk susceptibility, via their association with some MetS components as dyslipidemia, hyperglycemia, obesity, and hypertension. Nevertheless, we can state that genetic association and genetic susceptibility studies to MetS in North African populations are still lacking, requiring additional well-designed epidemiogenetic studies.

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

Cited by 4 publications

References 80 publications

Genetic and Epigenetic Association of Hepatocyte Nuclear Factor-1α with Glycosylation in Post-Traumatic Stress Disorder

Genetic and Epigenetic Association of Hepatocyte Nuclear Factor-1α with Glycosylation in Post-Traumatic Stress Disorder

Decoding the genetic relationship between Alzheimer’s disease and type 2 diabetes: potential risk variants and future direction for North Africa

Genetic Polymorphisms Associated with Metabolic Syndrome in North Africa: Systematic Review and Meta-Analysis

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