ECE2022 Poster Presentations Diabetes, Obesity, Metabolism and Nutrition (202 abstracts)
Combination study of apoptosis gene polymorphisms in mitochondrial diabetes: Potential role in the pathogenesis of mitochondrial diabetes
Faten Haj Kacem Akid 1 , Mohamed Abdellahi Mohamed Ahmed 1 , Dhieb Nesrine 1 , Youssef S 2 , Mkaouar-Rebai E 2 , Fakhfakh F 2 , Mouna Mnif 1 & Mohamed Abid 1
1Department of Endocrinology and Diabetology CHU Hedi Chaker Sfax, Tunisia; 2Laboratory of Molecular and Functional Genetics, Faculty of Science, University of Sfax, Tunisia
Introduction: Mitochondrial diabetes (DM) is a monogenic form of maternal transmission diabetes that is caused by mutations in the mitochondrial genome. These mutations affecting mitochondrial function may be the cause of initiation of the phenomenon of apoptosis itself having an aggravating role of the phenotype in patients with mitochondrial diabetes.
Materials and Methods: This study involved 43 patients with mitochondrial diabetes (20 non-syndromic and 23 syndromic) for whom mutations were identified in the mitochondrial genome in addition to 100 controls of the general Tunisian population. An analysis of apoptosis was carried out on muscle biopsy using TUNEL, immunohistochemistry and western blot cytochrome C expression. The analysis of 11 SNPs in 10 apoptosis genes (TP53, BCL2, BAX, BAK1, FASL, CASP8, CASP10, CASP3, CASP7) was carried out by genotyping on the DNA of patients and controls.
Results: Our results confirmed the presence of apoptosis by the TUNEL approach on muscle biopsy and by the study of the expression of the cytochrome C protein by western blot. This apoptosis is most accentuated in patients with a severe phenotype suggesting possible involvement of genetic factors. To study this hypothesis, we carried out a genotyping analysis of 11 functional SNPs in 9 genes involved in the pathways of apoptosis to evaluate their association with the development of apotosis in patients with DM compared with controls. Results showed that mitochondrial (TP53) apoptosis and effector pathway (PSAP3) SNPs were significantly associated with a high risk of developing apoptosis (TP53 rs 1042522 OR 3.57, PSAP3 rs1405937 OR 4.33). In addition, this risk is increased (TP53 rs 1042522 OR 6.07, CASP3, rs1405937 OR 4.8) in patients with syndromic DM and pathogenic mitochondrial mutations.
Conclusion: apoptosis initiated by mtDNA mutations is aggravated by SNPs of the apoptosis genes in particular Tp53, and CASP3 in patients with DM in comparison with controls of the general population.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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