MiR‐146a polymorphism is associated with asthma but not with systemic lupus erythematosus and juvenile rheumatoid arthritis in Mexican patients

Abstract

Extensive research has shown that aberrant expression of microRNAs (miRNAs) plays an important role in innate and adaptive immune responses. The rs2910164 polymorphism has been identified as a functional variant, which affects the transcription and expression level of miR-146a and, thereby, contributes to the pathogenesis of several inflammatory and autoimmune diseases. To investigate whether the rs2910164 G/C polymorphism was associated with asthma, systemic lupus erythematosus (SLE) or juvenile rheumatoid arthritis (JRA), we performed an association study in a pediatric Mexican cohort. We included 979 pediatric patients (asthma: 402, SLE: 367 and JRA: 210) and 531 control subjects without inflammatory or immune diseases. Genotyping was performed using the 5' exonuclease technique. The genotype distribution of the rs2910164 polymorphism was in Hardy-Weinberg equilibrium in each group. No significant differences were detected in the distribution of this polymorphism between cases and controls (P = 0.108, 0.609 and 0.553 for subjects with asthma, JRA and SLE, respectively). However, stratification by gender showed a statistically significant difference between asthmatic and control females, where the C allele was significantly associated with protection to asthma (odds ratio = 0.694, 95% confidence interval 0.519-0.929, P = 0.0138). Our results provide evidence that rs2910164 may play a role in the susceptibility to childhood-onset asthma, but not SLE or JRA in Mexicans. Further association studies may contribute to determining the role of miR-146a single-nucleotide polymorphisms in immune-mediated diseases.

Genetic Association of MiR-146a with Multiple Sclerosis Susceptibility in the Chinese Population

“…Several studies have examined the association between the miR-146a rs2910164 polymorphism and autoimmune diseases, including RA [8], SLE [8,9] and MS [19]. Although previous studies have suggested that many autoimmune diseases share common predisposing factors, the results are inconsistent [26].…”

“…In this study, the observation that females have a higher MS prevalence than males may result from an interaction between the genotype and sex hormones during development. Gender-dependent associations have been shown in other case-control studies involving immune entities [8]. As the miR-146a gene is located on 5q33.3, one of the richest loci for genes associated with autoimmune diseases, the linkage disequilibrium between rs2910164 and SNPs near miR-146a (such as rs2431697 and rs2277920) or in other candidate genes ( ADRB2, IL-12, IL-4, IL-13 ) should also be taken into consideration.…”

“…One of these conserved miRNAs is miR-146a, which is well known for its powerful regulation of immune response and inflammation. MiR-146a , located in the LOC285628 gene on human chromosome 5, is involved in modulating the negative regulation of Toll like receptor (TLR) signaling, airway remodeling-associated proteins (MMP-13 and collagen II), and pivotal inflammatory cytokines [8]. The dysregulation of miR-146a is associated with multiple autoimmune diseases, such as systemic lupus erythematosus (SLE) [9], rheumatoid arthritis (RA) [10], Sjogren's syndrome (SS) [11], and MS [12].…”

MicroRNAs in the key events of systemic lupus erythematosus pathogenesis

“…76 ). additionally, no association was found in two ethnicities included in the studies, namely caucasian -mexican and european 66,71,77 and asian -chinese Han nationality 66,67 .…”

Juvenile idiopathic arthritis and physical activity: Possible inflammatory and immune modulation and tracks for interventions in young populations

“…miR-146 is a negative regulator of signaling pathways in the Th1 response (TLR, TRAF-6 and IRAK1). It targets NFκB regulation by inhibiting IRAK1 and TRAF-6, leading to a reduction of the downstream production of various inflammatory mediators (TNFα and IL-1β) [102,[106][107][108][109][110]. The ERA subtype of JIA features an increased mRNA expression of IRAK4, IRAK1 and TRAF-6 in peripheral blood and synovial fluid mononuclear cells [111].…”