Limits...
Frequency of HNF4A-P.I463V Variant in the Tunisian North-African Population and Its Relation with Diabetes Mellitus.

Amara A, Ben Charfeddine I, Ghédir H, Mamaï O, Jemni-Yacoub S, Chaieb L, Saad A, Chadli-Chaieb M, Gribaa M - Iran. J. Public Health (2015)

Bottom Line: We also performed in-silico analysis using PolyPhen2 and Mutation T@sting softwares to assess the probable effect of HNF4A-p.I463V variant.HNF4A-p.I463V had a rare frequency in different populations and was found in 3 control subjects (1.5%) of the studied population.It is also present in different ethnicities and in- silico analysis showed conflicting results.

View Article: PubMed Central - PubMed

Affiliation: Unit of Molecular Endocrinology, Sousse Faculty of Medicine, University of Sousse, Sousse, Tunisia ; Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia ; Higher Institute of Biotechnology of Monastir, University of Monastir, Tunisia.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

The diabetic Caucasian and Tunisian families having HNF4A-p.I463V variant Filled and open symbols represent diabetic subjects and normal glucose tolerance individuals, respectively. The numbers under the symbols are the identification numbers. Below the numbers, it is the genotype at codon I463V: N, normal allele (Isoleucine); m, mutant allele (valine). Below the genotype is the diagnostic age of diabetes for affected members and age at examination, followed by the treatment for diabetes (OHA: Oral hypoglycemic agents and INS: Insulin). An arrow with P letter indicates the proband.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4402419&req=5

Figure 2: The diabetic Caucasian and Tunisian families having HNF4A-p.I463V variant Filled and open symbols represent diabetic subjects and normal glucose tolerance individuals, respectively. The numbers under the symbols are the identification numbers. Below the numbers, it is the genotype at codon I463V: N, normal allele (Isoleucine); m, mutant allele (valine). Below the genotype is the diagnostic age of diabetes for affected members and age at examination, followed by the treatment for diabetes (OHA: Oral hypoglycemic agents and INS: Insulin). An arrow with P letter indicates the proband.

Mentions: Performing a molecular diagnosis of monogenic diabetes is not an easy task because of its clinical and genetic heterogeneity (16). Some genetic variants could also be problematic such as HNF4A-p.I463V. In an earlier study, we found that HNF4A-p.I463V cosegregated with diabetes phenotype in a Tunisian family (Fig. 2 and Table 2). It was present in three patients from this family and was absent in two other non-affected relatives (13). Contrariwise, this variant didn’t show a perfect cosegregation in a Caucasian family (12). Hitherto, there is not enough information in the literature about HNF4A-p.I463V variant (rs147638455). It is not clear whether it is a mutation directly causing MODY-1 or just a non-synonymous polymorphism with low effect.


Frequency of HNF4A-P.I463V Variant in the Tunisian North-African Population and Its Relation with Diabetes Mellitus.

Amara A, Ben Charfeddine I, Ghédir H, Mamaï O, Jemni-Yacoub S, Chaieb L, Saad A, Chadli-Chaieb M, Gribaa M - Iran. J. Public Health (2015)

The diabetic Caucasian and Tunisian families having HNF4A-p.I463V variant Filled and open symbols represent diabetic subjects and normal glucose tolerance individuals, respectively. The numbers under the symbols are the identification numbers. Below the numbers, it is the genotype at codon I463V: N, normal allele (Isoleucine); m, mutant allele (valine). Below the genotype is the diagnostic age of diabetes for affected members and age at examination, followed by the treatment for diabetes (OHA: Oral hypoglycemic agents and INS: Insulin). An arrow with P letter indicates the proband.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4402419&req=5

Figure 2: The diabetic Caucasian and Tunisian families having HNF4A-p.I463V variant Filled and open symbols represent diabetic subjects and normal glucose tolerance individuals, respectively. The numbers under the symbols are the identification numbers. Below the numbers, it is the genotype at codon I463V: N, normal allele (Isoleucine); m, mutant allele (valine). Below the genotype is the diagnostic age of diabetes for affected members and age at examination, followed by the treatment for diabetes (OHA: Oral hypoglycemic agents and INS: Insulin). An arrow with P letter indicates the proband.
Mentions: Performing a molecular diagnosis of monogenic diabetes is not an easy task because of its clinical and genetic heterogeneity (16). Some genetic variants could also be problematic such as HNF4A-p.I463V. In an earlier study, we found that HNF4A-p.I463V cosegregated with diabetes phenotype in a Tunisian family (Fig. 2 and Table 2). It was present in three patients from this family and was absent in two other non-affected relatives (13). Contrariwise, this variant didn’t show a perfect cosegregation in a Caucasian family (12). Hitherto, there is not enough information in the literature about HNF4A-p.I463V variant (rs147638455). It is not clear whether it is a mutation directly causing MODY-1 or just a non-synonymous polymorphism with low effect.

Bottom Line: We also performed in-silico analysis using PolyPhen2 and Mutation T@sting softwares to assess the probable effect of HNF4A-p.I463V variant.HNF4A-p.I463V had a rare frequency in different populations and was found in 3 control subjects (1.5%) of the studied population.It is also present in different ethnicities and in- silico analysis showed conflicting results.

View Article: PubMed Central - PubMed

Affiliation: Unit of Molecular Endocrinology, Sousse Faculty of Medicine, University of Sousse, Sousse, Tunisia ; Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia ; Higher Institute of Biotechnology of Monastir, University of Monastir, Tunisia.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus