RESUMO
Type 2 diabetes mellitus (T2DM) is one of causes of mortality and morbidity in Moroccan population. The identification of genes implicated in this disease can help to found a specific treatment and to improve the quality of life for type 2 diabetic patients. In this study we analyze the association between a polymorphism (-308G>A) of TNF A promoter gene and T2DM in Moroccan patients. Five hundred and fifty-one individuals (307 patients with T2DM and 244 controls) were genotyped for this polymorphism by PCR-RFLP. This association was further reconsidered by a meta-analysis on 21 studies including 8,187 cases and 7,811 controls. We found that in Moroccan patients the -308A allele is strongly associated with T2DM (p = 0.000002; odds ratio 1.79, 95 % confidence interval 1.41-2.28). Based on our meta-analysis, there was no significant association detected between the TNF A -308G>A polymorphism and risk for T2DM. Our results suggest that the -308G>A polymorphism is a genetic risk factor for the development of T2DM in Moroccan population. On the other hand the meta analysis results led to controversial conclusions in other ethnicities.
Assuntos
Diabetes Mellitus Tipo 2/genética , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Idoso , Alelos , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Marrocos , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Regiões Promotoras Genéticas , Fatores de RiscoRESUMO
BACKGROUND: The goal of the study is to investigate the association between the APOA5 polymorphisms and haplotypes with Arterial Hypertension (AHT) in Moroccan patients. METHODS: The study was performed in 283 subjects, 149 patients with AHT and 134 controls. All subjects were genotyped for the APOA5 -1131 T > C (rs662799), 56C > G (rs3135506) and c.553G > T (rs2075291) polymorphisms. RESULTS: There was a strong association between -1131 T > C and 56C > G polymorphisms with AHT. The -1131 T > C and 56C > G polymorphisms were significantly associated with increased systolic blood pressure (SBP) and triglycerides (TG) levels. There were 4 haplotypes with a frequency higher than 5%, constructed from APOA5 polymorphisms, with the following order: -1131 T > C, 56C > G and c.553G > T. Haplotype H1 (TCG) was associated with decreased risk of AHT, whereas the haplotypes H2 (CCG) and H4 (CGG) were significantly associated with an increased risk of AHT. Carriers of H1 haplotype had a lower SBP and DBP and TG. In contrast, significant elevated SBP, DBP and TG were found in H4 haplotypes carriers. CONCLUSIONS: Our data demonstrate for the first time that several common SNPs in the APOA5 gene and their haplotypes are closely associated with modifications of blood pressure and serum lipid parameters in the AHT patient.
Assuntos
Apolipoproteínas A/genética , Hipertensão/genética , Polimorfismo Genético/genética , Adulto , Apolipoproteína A-V , Feminino , Predisposição Genética para Doença/genética , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Marrocos , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
PURPOSE: Retinoblastoma (RB), the most common intraocular tumor occurring in infancy and early childhood, is most often related to mutations in the RB1 gene. In this study, we screened the RB1 germline mutations in 41 unrelated Moroccan patients with retinoblastoma, 25 heritable cases, and 16 sporadic unilateral cases. METHODS: After complete ophthalmic examinations were performed and consent obtained, DNA was extracted from peripheral blood, and screening of RB1 mutations was performed with PCR direct sequencing of the promoter and the 27 coding exons of the RB1 gene. RESULTS: We identified ten germline mutations in 10/41 (24.39%) unrelated patients, among which three had not been previously reported. The mutation detection rate was 40% (10/25) in the heritable cases and 0% (0/16) in the sporadic unilateral cases. Of these mutations, six were nonsense, and three were frameshifts, all associated with severe phenotypes resulting in bilateral and multifocal tumors. One splice site mutation was found in a familial case associated with a low expressivity phenotype resulting in unilateral and unifocal tumors. Moreover, eight intronic variants were identified, three of which were novel. CONCLUSIONS: This first report of RB1 gene screening in Moroccan patients with retinoblastoma shows a comparable mutational spectrum to those reported previously, which has evident importance for managing patients with retinoblastoma and their families.