RESUMEN
BACKGROUND: Thalassemia is one of the most prevalent worldwide autosomal recessive disorders characterized by a great molecular and clinical expression heterogeneity. Alpha and beta-thalassemia are the main two types observed in case of mutations affecting alpha and beta-globin genes respectively. Delta-thalassemia is noted when mutations occur on the delta-globin gene. In Tunisia, ß-thalassemia prevalence is estimated at 2.21% of carriers. However, few reports investigated the delta-globin gene. OBJECTIVES: In this work, we aimed to perform a molecular study to help define the molecular spectrum of δ-thalassemia mutations in Tunisia. PATIENTS AND METHODS: The study involved 7558 patients among whom we selected 179 individuals with abnormal HbA2 values or fractions. Hemoglobin analysis was performed using Capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC). DNA sequencing was performed on ABI prism 310 Genetic Analyzer Applied Biosystems. CUPSAT (Cologne University Protein Stability Analysis Tool) was used for the prediction of protein stability changes upon missense mutations and mutants were modeled via DeepView-SwissPdbViewer and POV-Ray softwares for molecular dynamics simulation studies. RESULTS: We identified four mutations: HbA2-Yialousa described for the first time in Tunisia ( in 72.72% of cases) and 3 mutations reported for the first time in the world: (i) c.442 T > C Stop147Arg ext 15aa-stop observed in 18.18% of cases, (ii) c.187 G > C (Ala62Pro) noted in 4.54% of cases and (iii) c.93-1G > C found in 4.54% of cases. CONCLUSION: Our data provide genetic basis that would be especially useful in screening for beta-thalassemia trait during delta-beta thalassemia associations.
Asunto(s)
Globinas delta/genética , Talasemia delta/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Secuencia de Bases/genética , Femenino , Frecuencia de los Genes/genética , Hemoglobina A2/genética , Hemoglobinas/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Análisis de Secuencia de ADN/métodos , Túnez/epidemiología , Globinas beta/genética , Talasemia beta/genética , Globinas delta/metabolismo , Talasemia delta/metabolismoRESUMEN
Vitamin D (VD) cannot be considered as a true vitamin, but rather as a hormone, which exerts its action via a vitamin D receptor (VDR). Many genes have been shown to be involved in the evolution of diabetes in various populations, such as the vitamin D receptor gene. The aim of our study was to investigate if BsmI, TaqI, ApaI, FokI, and Tru9I, polymorphisms of VDR gene have an impact on MODY diabetes and its clinical aspects in a Tunisian population. A total of 95 patients and 153 controls were genotyped using PCR-RFLP. The comparison of the allelic and genotypic frequencies of the five polymorphisms between MODY subjects and control groups revealed the association of MODY diabetes with TaqI, Tru9I and BsmI polymorphisms and no significant differences were observed in the distributions for the ApaI and FokI polymorphisms. After stratification with biochemical and clinical parameters and TaqI, Tru9I and BsmI polymorphisms, we found an association between the three SNPs and different parameters such as age of diagnosis, therapy, hsCRP and HDL-C levels. Our results revealed that TaqI, Tru9I and BsmI polymorphisms may be more related to the progression of MODY diabetes. The possible role of vitamin D in the pathogenesis of MODY is far from being completely understood. Further knowledge on this issue may identify new candidate targets in the treatment and prevention of the disease. Our findings suggest that the TaqI, Tru9I and BsmI polymorphisms may be more related to the progression of MODY diabetes.
