ABSTRACT
Background: Methotrexate (MTX) is one of the most common medications used for rheumatoid arthritis (RA) treatment. Single-nucleotide polymorphisms (SNPs) could potentially predict variability in therapeutic outcomes. Aim: This study aims to assess the impact of SNPs in genes encoding for the MTX pathway for predicting clinical and therapeutic responses to MTX in a cohort of Egyptian patients with RA. Subjects and Methods: Data from 107 Egyptian RA patients (aged 44.4 ± 11.4 years) treated with MTX monotherapy, for a duration of 3.7 ± 3.3 years, were collected. Genotypes of 10 SNPs from four different genes were analyzed using the allelic discrimination PCR technique. Results: The ATIC rs3821353 G/T (p = 0.034) and the C/T and C/C of SLC19A1 rs7279445 (p = 0.0018) were associated with a non-response to MTX, while DHFR rs10072026 C/T and C/C were associated with a good response (p < 0.001). Carriers of the ATIC rs382135 3 G (p = 0.001) and ATIC rs4673990 G (p < 0.001) alleles were more likely to develop RA, while the SLC19A1 rs11702425 T (p < 0.001) and GGH rs12681874 T (p = 0.003) allele carriers were more likely to be protected against RA. Carriers of the ATIC rs4673990 A/G genotype (p < 0.001) were at risk of developing RA, while carriers of the following genotypes were mostly protected against RA: ATIC rs3821353 T/T (p < 0.001), ATIC rs3821353 G/G (p = 0.004), SLC19A1 rs11702425 T/T (p = 0.001), SLC19A1 rs11702425 C/T (p = 0.003), GGH rs12681874 C/T (p = 0.004) and GGH rs12681874 T/T (0.002). Conclusion: The genotyping of genes involved in the MTX pathway may be helpful to predict which RA patients will/will not benefit from MTX, and thus, may help to apply a personalized medicine approach in RA.
ABSTRACT
HCV infection represented a foremost communal health trouble and Egypt has the largest epidemic of HCV in the world with prevalence of 14.7% for HCV antibody and 9.8% HCV-RNA. Nitric oxide (NO) is a signaling molecule participated in inhibiting of microbial diseases. Pro-inflammatory stimuli can trigger resting cells to produce inducible nitric oxide synthase ((iNOS) also referred to as (NOS2), which is very crucial for host response to contagious agents. NOS2A gene haplotypes has been associated with a number of diseases. This study aimed to assess the relation between NOS2A gene haplotypes and HCV treatment response in pegylated interferon alpha /ribavirin (PEG-IFN /RBV) in chronic HCV patients (CHC) in an attempt to find a predictor biomarker to detect poor responders to therapy. DNA was extracted from blood samples and subjected to detection of NOS2A gene haplotypes using real time PCR. Non-responder patients showed statistically significant higher percentages of unclassified haplotypes than responder patients (85.7% versus 58.6%, respectively) (P < 0.0001) and of haplotypes 4 and 5 (GTT and ATC) than non-responder patients (25.7% and 14.3% versus 0% and 0%, respectively) (P < 0.0001). The NOS2A gene haplotypes were not associated with response to PEG-IFN /RBV at 12th week Early Virological Response (EVR). In conclusion, NOS2A gene haplotypes are not considered predictors of response to PEG-IFN /RBV treatment. Further studies are required to elucidate predictor markers.
