MiR-146a G/C rs2910164 variation in South African Indian and Caucasian patients with psoriatic arthritis

Abstract

BackgroundPsoriasis and psoriatic arthritis (PsA) are inflammatory associated autoimmune disorders. MicroRNA (miR)-146a plays a crucial role in regulating inflammation. A single nucleotide polymorphism in the miR-146a gene (rs2910164), aberrantly alters its gene expression and linked with the pathogenesis of several disorders, including psoriasis and PsA. In South Africa, psoriasis and PsA are extremely rare in the indigenous African population and most common in both the Indian and Caucasian population. The aim of this study was to investigate whether the miR-146a rs2910164 contributes towards psoriasis and PsA development in South African Indian and Caucasian patients.MethodsSouth African Indian (n = 84) and Caucasian (n = 32) PsA patients (total n = 116) and healthy control subjects (Indian: n = 62 and Caucasian: n = 38; total n = 100) were recruited in the study. DNA was extracted from whole blood taken from all subjects, and genotyped for the miR-146a rs2910164 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Data for laboratory parameters were obtained from pathology reports. The consulting rheumatologist collected all other clinical data.ResultsUnstratified data (Caucasians + Indians): A significant decrease in C-reactive protein (CRP) levels in PsA patients was observed (CRP monitored at inclusion vs. after 6 months of treatment) (18.95 ± 2.81 mg/L vs. 9.68 ± 1.32 mg/L, p = 0.0011). The miR-146a rs2910164 variant C-allele frequency in PsA patients was significantly higher vs. healthy controls (35.78% vs. 26% respectively, p = 0.0295, OR = 1.59 95% CI 1.05–2.40). Stratified data (Indians): The variant C-allele frequency in Indian PsA patients was significantly higher vs. healthy Indian controls (35.71% vs. 22.58%, p = 0.0200, OR = 1.91 95% CI 1.13–3.22). Stratified data (Caucasians): The variant C-allele frequency distribution between Caucasian PsA patients and healthy Caucasian controls was similar.ConclusionThe rs2910164 variant C-allele may play a role in the progression of PsA in the South African Indian population. The main limitation in this study was the small sample size in the case-control cohorts, with a low overall statistical power (post-hoc power analysis = 19%).

Serum MicroRNA Signature as a Diagnostic and Therapeutic Marker in Patients with Psoriatic Arthritis

“…However, further experiments are required to elucidate the pathogenic mechanism of action of miR-21-5p in PsA pathogenesis. In support of the observations made in the present study, recent reports demonstrate elevated expression of miR-146a-5p in CD14+ monocytes from patients with PsA compared to both psoriasis patients and HC 35 , and that a single-nucleotide polymorphism in the miR-146a gene was associated with the progression of PsA 36 , an association that appears to be functional in patients with PsA but not RA 37 . Further, in terms of therapeutic response, elevated serum levels of miR-130a-3p in patients with ovarian cancer have been associated with therapeutic resistance to cisplatin 38 , which is consistent with other reports in glioblastoma patients and their response to a temazolamide treatment regimen 6 .…”

Association of rs2910164 polymorphism in MiR-146a gene with psoriasis susceptibility

“…Four articles containing 5 studies were included in the present meta-analysis. [17–20] The included studies were conducted in Greece, [17] South Africa, [18] Sweden, [19] and China, [20] respectively. The detailed information of all studies was displayed in Table 1.…”

“…All these evidences suggested that the G-allele of rs2910164 in miR-146a might play a pivotal role in the pathogenesis of psoriasis. However, Maharaj et al 's [18] study showed the opposite results. They found that C-allele of rs2910164 in psoriasis patients was significantly higher than healthy controls.…”

Association of microRNAs genes polymorphisms with arthritis: a systematic review and meta-analysis

“…Recently, studies assessing miR-146a rs2910164 or miR-499 rs3746444 polymorphism and risk of RA have been published [23–25], but the results are not always consistent. And other studies add to the evidence base of the associations of other miRNA polymorphism with arthritis risk but are not limited to RA – but not exclusively – the amount and impact of inflammation [24,26]. Therefore, we aimed to perform a systematic review and meta-analysis to systematically evaluate the relationship between miRNA polymorphism and arthritis risk, which can provide a further reference for finding excellent biomarkers and potential therapeutic targets of arthritis.…”