Frequency of IL28B rs12979860 single-nucleotide polymorphism alleles in newborn infants and in patients with chronic hepatitis C in Morocco.

BACKGROUND: Epidemiological and experimental evidence support the role of host genetics in treatment response and viral clearance in chronic hepatitis C (CHC). Recently, the CC genotype of IL28B single-nucleotide polymorphism (SNP) rs12979860 has been associated with spontaneous viral clearance and a better treatment response. The distribution of this polymorphism varies according to populations. Frequency of rs12979860 SNP alleles in the Moroccan population is unknown. The aim of our study was to estimate the frequency of the C allele of this SNP in the Moroccan population and, in parallel, in a cohort of Moroccan patients with CHC treated with pegylated interferon-alpha and ribavirin. METHODS: We used real-time polymerase chain reaction assay based on TaqMan technology to determine the allele frequency of the rs12979860 SNP in 100 Moroccan newborn infants. We also compared the frequency of the CC genotype between two groups of patients with genotype 1-CHC treated by combination therapy: group1, n=30 patients, responders who achieved sustained viral response (SVR) and group2, n=30 patients, nonresponders. RESULTS: The rs12979860 C allele frequency was estimated to be 73% in the Moroccan population. The frequency of this allele in the group of patients with CHC was only 58.3%, and the CC genotype is more prevalent in group1 (62.5%) than in group 2. CONCLUSIONS: This is the first report providing genetic data related to the frequency of genetic polymorphisms of IL28B in Morocco. The C-allele frequency of the IL28B gene SNP rs12979860 in Morocco is higher than in the African populations. Distribution of this SNP distinguishes in a population of CHC between SVR and nonresponders. This result merits consideration and should be studied by analyzing a larger sample size of patients.

Frequencies of CYP3A5*1/*3 variants in a Moroccan population and effect on tacrolimus daily dose requirements in renal transplant patients.

The cytochromes P450 are a superfamily of oxidative enzymes, which are implicated in the metabolism of a large number of endogenous substances as well as exogenous chemicals. The cytochrome P450 (CYP3A5) appears to play an important role in drug metabolism activity. The most frequent mutation in the CYP3A5 gene, affecting its activity, consists of a G6986A transition within intron 3. In this study, we determined the allelic frequency of CYP3A5*3 in a Moroccan population, consisting of 108 individuals including 10 renal transplant patients. About 8.33% (9/108) of the subjects were homozygous wild-type (CYP3A5*1/*1), 37.04% (40/108) were heterozygous (CYP3A5*1/*3), and 54.63% (59/108) were homozygous (CYP3A5*3/*3). Therefore, CYP3A5*3 variant was the most frequent allele detected at 73.15%. In the second part of this work, we assessed the influence of the CYP3A5 polymorphism on tacrolimus doses required for 10 renal transplant patients who are receiving tacrolimus as immunosuppressive therapy. Our results showed that, during the first 3 months after kidney transplantation, the tacrolimus daily requirements for heterozygous patients (CYP3A5*3/*1) were higher compared with homozygous patients (CYP3A5*3/*3) (0.133 ± 0.026 vs. 0.21 ± 0.037 mg/kg/day). After the third month the difference was also observed, whereby the mean of tacrolimus daily requirements for patients with CYP3A5*3/*3 and CYP3A5*1/*3 was 0.053 ± 0.013 and 0.08 ± 0.014 mg/kg/day, respectively. This first study in Morocco provides genetic data related to the frequency of genetic polymorphisms of CYP3A5 and opens the perspective to develop other pharmacogenetic studies.