Association study of obesity susceptibility gene polymorphisms in relation to 5 tunisian families

Hamdi Frikha; Hana Charfi; Yassmine Abdelkafi; Khouloud Boujelben; Salah Dhoha Ben; Kacem Akid Faten Haj; Nadia Charfi; Fatma Mnif; Mouna Mnif; Faiza Fakhfakh; Mouna Elleuch; Mohamed Abid; Majdoub Nabila Rekik

doi:10.1530/endoabs.99.EP62

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Endocrine Abstracts (2024) 99 EP62 | DOI: 10.1530/endoabs.99.EP62

ECE2024 Eposter Presentations Diabetes, Obesity, Metabolism and Nutrition (383 abstracts)

Association study of obesity susceptibility gene polymorphisms in relation to 5 tunisian families

Hamdi Frikha ¹ , Hana Charfi ¹ , Yassmine Abdelkafi ¹ , Khouloud Boujelben ¹ , Dhoha Ben Salah ¹ , Faten Haj Kacem Akid ¹ , Nadia Charfi ¹ , Fatma Mnif ¹ , Mouna Mnif ¹ , Faiza Fakhfakh ² , Mouna Elleuch ¹ , Mohamed Abid ¹ & Nabila Rekik Majdoub ¹

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¹Hedi Chaker University Hospital, Department of Endocrinology; ²University of Sfax, Laboratory of Molecular and Functional Genetics, Tunisia

Introduction: Obesity, in its common form, exhibits extreme genetic heterogeneity, and its mode of transmission remains unknown. To investigate the impact of the genetic component, we conducted an association study between polymorphisms of functional and positional candidate genes: Leptin and its receptor gene (LEP, LEPR), Melanocortin 4 Receptor (MC4R), FTO gene: Fat mass and associated obesity, and Pro-opiomelanocortin gene (POMC); with obesity and associated phenotypes (anthropometric and metabolic parameters, insulin levels, leptin levels, Homeostatic Model Assessment of Insulin Resistance HOMA-IR).

Materials and Methods: Our study included 50 patients from 5 Tunisian families affected by obesity and 52 controls from the Tunisian population. Genotyping of candidate gene single nucleotide polymorphisms (SNPs) was performed using PCR-RFLP and automatic sequencing. The association study was conducted using the Family-Based Association Test (FBAT).

Results: Statistical analysis of the genotyping results for different polymorphisms of the LEP gene showed that the SNPs (H1328084 A>G and +19 G>A), located in the 5’ region of the gene, are associated with hyperleptinemia. In silico analyses demonstrated that these two polymorphisms could affect potential binding sites for certain transcription factors (c-Myb for A19G and NF-1 for H1328084) and consequently could play an important role in the regulation of plasma leptin levels. Regarding the LEPR gene, we found that the G allele of the c.A668G (Q223R) polymorphism is significantly associated with hyperinsulinemia and hyperleptinemia. Our results also showed that the Rsal variant of the POMC gene is associated with anthropometric parameters, plasma cholesterol levels, and blood pressure. Additionally, an association was detected with diastolic blood pressure and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) for another 3’UTR polymorphism of the POMC gene (C8246T). Finally, no significant association was detected for the MC4R and FTO genes.

Discussion and Conclusion: The study of the genetic variability of the candidate genes in 5 Tunisian families confirms the association between the two functional leptin gene polymorphisms (H1328084 A/G and A19G) and the Q223R polymorphism of the leptin receptor gene LEPR with hormonal parameters. Only the C8246T polymorphism of the POMC gene seems to be associated with insulin resistance. A larger sample size study and inclusion of sporadic cases could better establish the impact of various genetic variants, particularly the MC4R and FTO genes.