Most currently known breast cancer predisposition genes play a role in DNA repair by homologous recombination. Recent studies conducted on RAD51 paralogs, involved in the same DNA repair pathway, have identified rare germline mutations conferring breast and/or ovarian cancer predisposition in the RAD51C, RAD51D and XRCC2 genes. The present study analysed the five RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3) to estimate their contribution to breast and ovarian cancer predisposition.

Background: Circulating non-coding RNAs (ncRNAs) have been implicated in health and disease. This study aimed to evaluate the serum expression profile of microRNA-499a (miR-499a) and its selected bioinformatically predicted partner long-ncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) in diabetes-related end-stage renal disease (ESRD) patients and to correlate the expressions with the patients' clinicolaboratory data. Subjects and methods: Real-time quantitative polymerase chain reaction was applied in diabetics with and without ESRD (n = 90 for each). Results: Serum MALAT1 expression levels were increased in the ESRD group relative to diabetics without ESRD with median (quartile) values of 10.5 (1.41–126.7) (p < .001). However, miR-499a levels were decreased in more than half of ESRD patients with a median of 0.96 (0.13–3.14). Both MALAT1 and miR-499a expression levels were inversely correlated in the ESRD patient-group. Conclusions: MALAT1 up-regulation and miR-499 down-regulation might be involved in diabetic nephropathy-related ESRD pathogenesis. Functional validation studies are warranted to confirm the MALAT1/miR-499a partnership.

Small non-coding RNAs (microRNAs) have been evolved to master numerous cellular processes. Genetic variants within microRNA seed region might influence microRNA biogenesis and function. The study aimed at determining the role of microRNA-499 (MIR-499) gene family polymorphism as a marker for susceptibility and progression of bronchial asthma and to analyze the structural and functional impact of rs3746444 within the seed region. Genotyping for 192 participants (96 patients and 96 controls) in the discovery phase and 319 subjects (115 patients and 204 controls) in the replication phase was performed via Real Time-Polymerase Chain Reaction technology. Patients underwent the methacholine challenge test and biochemical analysis. Gene structural and functional analysis, target prediction, annotation clustering, and pathway enrichment analysis were executed. Predicted functional effect of rs37464443 SNP was analyzed. miR-499 gene family is highly implicated in inflammation-related signaling pathways. Rs374644 (A > G) in MIR499A and MIR499B within the seed region could disrupt target genes and create new genes. The G variant was associated with high risk of developing asthma under all genetic association models (G versus A: OR = 3.27, 95% CI = 2.53–4.22; GG versus AA: OR = 9.52, 95% CI = 5.61–16.5; AG versus AA: OR = 2.13, 95% CI = 1.24–3.46; GG + AG versus AA: OR = 4.43, 95% CI = 2.88–6.82). GG genotype was associated with poor pre-bronchodilator FEV₁ (p = 0.047) and the worst bronchodilator response after Salbutamol inhalation, represented in low peaked expiratory flow rate (p = 0.035). miR-499 rs3746444 (A > G) polymorphism was associated with asthma susceptibility and bronchodilator response in Egyptian children and adolescents. Further functional analysis is warranted to develop more specific theranostic agents for selecting targeted therapy.