Tehran University of Medical Sciences Iranian Journal of Public Health 2251-6085 44 3 2015 03 15 396 403 Abdelbasset Amara Unit of Molecular Endocrinology, Sousse Faculty of Medicine, University of Sousse, Sousse, Tunisia AND Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia AND Higher Institute of Biotechnology of Monastir, University of Monastir, Tunisia. Ilhem Ben Charfeddine Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia AND Higher Institute of Biotechnology of Monastir, University of Monastir, Tunisia. Houda Ghédir Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia AND Higher Institute of Biotechnology of Monastir, University of Monastir, Tunisia. Ons Mamaï Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia AND Higher Institute of Biotechnology of Monastir, University of Monastir, Tunisia. Saloua Jemni-Yacoub Regional Center of Blood Transfusion of Sousse, Sousse, Tunisia. Larbi Chaieb Dept. of Endocrinology and Diabetology, Farhat Hached University Hospital, Sousse, Tunisia. Ali Saad Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia. Molka Chadli-Chaieb Unit of Molecular Endocrinology, Sousse Faculty of Medicine, University of Sousse, Sousse, Tunisia AND Dept. of Endocrinology and Diabetology, Farhat Hached University Hospital, Sousse, Tunisia. Moez Gribaa Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia. 2015 10 14 Background: HNF4A-p.I463Vvariant, reported previously in two distinct families suspected of MODY-1, is assessed in this report to determine whether it is a mutation or a polymorphism (frequency >1%). Methods: 200 Tunisian healthy people were screened for the presence of HNF4A-p.I463V variant, using RFLP-PCR technique and sequencing. Then, the frequency of this variant was estimated in the Tunisian population and compared to other populations registered in genetic databases. We also performed in-silico analysis using PolyPhen2 and Mutation T@sting softwares to assess the probable effect of HNF4A-p.I463V variant. Results: HNF4A-p.I463V had a rare frequency in different populations and was found in 3 control subjects (1.5%) of the studied population. PolyPhen2 predicted that it is a polymorphism, whereas mutation T@sting suggested a probably affected mutant protein. Conclusion: HNF4A-p.I463V has a relatively high frequency (>1%) in our control cohort. It is also present in different ethnicities and in- silico analysis showed conflicting results. For these reasons, HNF4A-p.I463V should not be considered as a mutation responsible for MODY-1. https://ijph.tums.ac.ir/index.php/ijph/article/view/3633 https://ijph.tums.ac.ir/index.php/ijph/article/download/3633/3308