Crosstalk between miR-146a and pro-inflammatory cytokines in patients with systemic lupus erythematosus.

microRNA-146a (miR-146a) plays an essential role in immune anomalies and organ injury of systemic lupus erythematosus (SLE) by regulating the disease's inflammation and complications. Here, we analyzed the expression of miR-146a in SLE and a panel of pro-inflammatory cytokines (IL-1, IL-6, IL-8, IL-17, and TNF-α). Association between all measured parameters and the disease's clinical manifestation and response to treatment was monitored. Our study populations were 113 SLE patients and 104 healthy volunteers. miR-146a expression in peripheral blood mononuclear cells (PBMCs) was measured by quantitative real-time PCR (RT-qPCR). The content of the plasma cytokines (IL-1ß, IL-6, IL-8, IL-17, and TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA). Compared with healthy controls, miR-146a expression was significantly increased (p < 0.05) in lupus patients. The analysis of the receiver operator characteristic curve (ROC) of miR-146a showed 91% sensitivity and 70% specificity. IL-1ß, IL-6, and IL-17 cytokines were significantly increased (p < 0.001), while IL-8 and TNF-α were significantly decreased (p < 0.001) in SLE patients against controls. The expression of miR-146a and TNF-α was upregulated considerably in SLE patients with severe disease activity. miR-146a expression was positively correlated with IL-6. Our results pointed to the elevation of miR-146a as a trade marker of SLE patients. Reduction of IL-8 and TNF-α in combination with an elevation of IL-1ß, IL-6, and IL-17 might refer to miR-146a's dual effect in controlling inflammation in lupus. Although we shed some light on the role of miR-146a in SLE, further study is recommended to improve our results.

mir-146a genetic polymorphisms in systemic lupus erythematosus patients: Correlation with disease manifestations.

This study aimed to investigate the genetic polymorphisms of miR-146a SNPs (rs2910164, rs57095329, and rs2431697) in systemic lupus erythematosus (SLE) patients and their association with clinical manifestations. The implication of SNPs on miR-146a expression level was also evaluated. SLE patients (113) and healthy controls (104) were registered in this study. The miR-146a SNPs were genotyped by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Quantitative real-time PCR was used to measure the miR-146a expression in peripheral blood mononuclear cells (PBMCs). Our results showed that the genotype frequency of miR-146a SNPs didn't deviate significantly from the Hardy-Weinberg equilibrium (HWE). The AG genotype and G allele of miR-146a (rs57095329 A/G) might be considered a risk factor for the disease (OR = 2.27; CI: 0.78-6.57 and OR: 2.35; CI: 0.79-6.92 for AG genotype and G allele, respectively). Although, no statistical significance in the distribution of miR-146a SNPs (rs2910164, rs57095329, and rs2431697) was found, indicating the lack of association between the three SNPs and SLE susceptibility. Significantly, the higher frequency of the AA genotype of miR-146a (rs57095329) was associated with pancytopenia (P < 0.05), while the CT genotype of miR-146a (rs2431697) was associated (P < 0.05) with the antiphospholipid syndrome (APS). SLE patients had significantly higher levels of miR-146a compared to controls (P < 0.05). Elevation of miR-146a was independent of any SNP genotypes. In conclusion, this pilot study shows no association between miR-146a SNPs in our population group and susceptibility to lupus. Studies concerning other miRNAs in larger sample sizes are essential for a better understanding of their role in susceptibility to SLE disease.

Genetic polymorphisms of IL-27 and risk of systemic lupus erythematosus disease in the Egyptian population.

OBJECTIVE: Cytokine polymorphisms have been associated with systemic lupus erythematosus (SLE) pathogenicity. Interleukin 27 (IL-27) is an important one of pro-/anti-inflammatory cytokine. It has been reported in various Th1/Th17-mediated inflammatory disorders, and even in Th2-complexed diseases, such as SLE. In our preliminary study, the aim was to investigate the potential roles of single nucleotide polymorphism (SNP) -964A/G (rs153109) and + 2905 T/G (rs17855750) in an IL-27p28 gene on susceptibility to SLE. METHODS: The 112 Egyptian SLE patients against 101 healthy persons were enrolled in this work. The polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) is used for genotyping IL-27 SNPs. RESULTS: No significant variations were found between patients and control in the genotype and allele frequencies of IL-27p28 (-964A/G). SLE patients have a significant increase in the frequency of IL-27p28 (+ 2905 T/G) TG genotype (P < 0.01) and G allele (P < 0.01) compared to controls. Complete disappearance of GG genotype was demonstrated in both groups. G allele might have considered a disease risk factor with odd ration (OR) = 9.184. From four possible haplotypes, the frequency of AT haplotype elevated in both examined groups. CONCLUSION: This was the first study on the Egyptian population for studying the relation between IL-27 SNPs and SLE. Our preliminary study indicated that both TG genotype and G allele of IL-27p28 (+ 2905 T/G) could consider risk factors for SLE. Key Points • This article provides an information about the relation between systemic lupus erythematosus and interleukin-27 cytokine by detection single nucleotide polymorphism.

Association of C3435T, C1236T and C4125A Polymorphisms of the MDR-1 Gene in Egyptian Children with Acute Lymphoblastic Leukaemia

Background: P-glycoprotein (P-gp), a membrane transporter encoded by the multidrug resistance-1 (MDR1) gene, influences pharmacokinetics and metabolism of anticancer drugs and contributes to multidrug resistance phenotype in acute lymphoblastic leukemia (ALL). Genetic variation ofMDR1 in ALL patients is increasingly recognized as a factor influencing response to treatment. Aim: To investigate the possible role of MDR-1 gene polymorphisms (C3435T, C1236T and C4125A) as risk factors for the development and clinical outcome of ALL in Egyptian children. Materials and Methods: Genotyping of MDR-1 C3435T, C1236T and C4125A single nucleotide polymorphisms (SNPs) was accomplished using a polymerase chain reaction­restriction fragment length polymorphism (RFLP-PCR) assay with 120 childhood ALL patients and 100 healthy controls. Results: Homozygous T with the C3435T SNP showed a protective effect as compared to homozygous C (OR=0.748) while heterozygous CT correlated with a poor outcome (high risk, drug unresponsiveness, relapse and high percentage of death). Additionally, the T allele of the C1236T SNP showed a significant relation with ALL risk (OR=1.6). However, there were no significant differences in the genotype and allele frequencies of MDR-1 SNPs between patients and controls. Only one genotype (CC) and one allele of MDR-1 (C4125A) were seen. Neither CA/AA genotypes nor A alleles were present in ALL patients and normal controls. TC was the predominant haplotype in both groups, while CT proved to be minor. The cumulative incidence of relapse was higher with the CC genotype of C1236T as compared with TT. Conclusion: From our preliminary data, the CT genotype of C3435T is associated with a poor ALL outcome while the CC genotype of C1236T is related with an increased incidence of relapse. Although our results provide assistance for oncologist choice of individual therapeutic strategy taking the patient genetic repertoire into consideration, further investigations with larger sample size should be conducted to validate our results.