ABSTRACT
The UDP-glucuronosyltransferase 1A1 gene that encode the enzyme UGT1A1 responsible for glucuronidation undergoes several variations that may affect the enzymatic activity or expression and which are the cause of metabolic disorders related to the glucuronidation of bilirubin, such as Gilbert's syndrome and Crigler Najjar's syndrome. Among the most common variations, there is the repeat polymorphism A [TA] n TAA in TATA box and biallelic mutation G211A in exon 1. We consider in this work to determine their frequencies in a healthy population. The polymorphism A [TA] n TAA showed that genotype [TA7/TA7] was described as being associated with Gilbert's syndrome and was encountered in 11% of the population studied. This percentage is close to the value described in the Caucasian population, estimated at 10%. Concerning the polymorphism G211A, our results show that the mutated allele is encountered in 15.7% of our study population. This frequency differs greatly from that reported for Caucasians and Afro-Americans but it is similar to that perceived at the Japanese. All these results suggest that the Tunisian population appears to be heterogeneous view UGT1A1 gene mutation status. Regarding the origins and distribution of such polymorphisms in our population, the study reveals a high haplotypic heterogeneity and emergence of the particular haplotype [TA] 6-G considered ancestral. The comparison of the haplotype structure generally leads to the development of a hypothetical tree of the origin and spread of different haplotypes
ABSTRACT
The hearing loss is a problems of public health which can be described as major from the economic and human point of view, since 1 child over 1000 has at the birth a severe or profound deafness. This deafness has a prevalence of 1 per 10 in certain Tunisian geographical isolates. Our work concerned 33 patients with nonsyndromic sensorineural deafness who are regarded as probands and are recruited in service ORL of the Hospital La Rabta of Tunis. For each patient, a family investigation was carried out in residence and complete pedigrees were established. In addition, we selected a sample of 320 unaffected subjects for whom we established pedigrees in order to compare their inbreeding coefficient with that of the patients The samples of this study are orginated from the governorate of Bizerte The segregation analysis by the method of the maximum likelihood applied to the sample of deafs allowed to estimate the segregation frequency by taking account of various modes of selection in the sibships. The results obtained are compatible with autosomic recessive model with complete penetrance of the gene. The recessive hypothesis is strenghthened by the increase in the inbreeding coefficient of the probands compared to that of the controls