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

Abstract

Background: miR-146a polymorphisms have been involved in susceptibility to multiple diseases. The aim of the present study was to analyze the potential association between two functional miR-146a polymorphisms (rs2910164 and rs57095329) and multiple sclerosis (MS) in the Han Chinese population. Methods: A cohort of 525 patients and 568 healthy controls were genotyped to detect the two polymorphisms by SNaPshot. Results: No significant differences were detected in the distribution of the two miR-146a polymorphisms between the patients and controls (P > 0.05). However, stratification by gender showed a statistically significant difference in the frequency of the genotype rs2910164 between MS patients and control females (P=0.009). Further stratification analysis by subgroup revealed that the miR-146a rs2910164 C allele conferred a higher risk of developing relapsing-remitting MS (RRMS) (P=0.018). In addition, the rs2910164 C allele was significantly associated with increased expression of miR-146a in patients with RRMS (P=0.025). Moreover, patients with the rs2910164 C allele released more TNF-α and IFN-γ, but not IL-1β, compared with individuals carrying the homozygous GG genotype (P < 0.05). Conclusions: Our results provide evidence that rs2910164 may play a role in MS susceptibility in females. The rs2910164 G>C variation may affect the expression of miR-146a and the release of proinflammatory cytokines.

Les microARN

“…Deux théories qui s'opposent l'une à l'autre, émergent. La première considère la dérégulation des miARN comme un des facteurs responsables de l'apparition de la SEP. À l'appui de cette théorie, la mise en évidence récente de l'association entre SEP et certains variants génétiques de miARN [9,10]. La seconde théorie suppose que la dérégulation des miARN serait une conséquence d'un dérèglement préalable de la réponse neuro-immune.…”

“…Au début des années 2000, l'importance des miARN a été décrite dans diffé-rents contextes pathologiques (le diabète [6] (➜), les maladies cardiovasculaires [7,58] (➜) et le cancer [8]). Plusieurs équipes se sont alors intéres-sées à l'expression des miARN chez les patients atteints de SEP. D'autres ont étudié les polymorphismes des gènes codant ces miARN : des polymorphismes mononucléo-tidiques (ou SNP pour single nucleotide polymorphism) associés à la SEP ont ainsi été découverts dans certains gènes de miARN [9,10]. Parallèlement, un vaste réseau de miARN, dont l'expression est modifiée chez les patients atteints de SEP, a été mis en évidence, princiconséquence, des recommandations récentes ont proposé de regrouper la PPMS et la SPMS en une seule entité, dénommée « maladie progressive ».…”

MicroRNA-146a rs2910164 is associated with severe preeclampsia in Black South African women on HAART

“…MicroRNAs (miRNAs; miRs) are small (±22 nucleotides), endogenous, non-coding RNA’s that regulate gene expression by modulating the expression of multiple target mRNAs, inducing either translational inhibition or mRNA degradation [15]. They are involved in various pathological processes [15], including the regulation of innate and adaptive immune responses [16].…”

“…They are involved in various pathological processes [15], including the regulation of innate and adaptive immune responses [16]. MiRNA-146a is involved in modulating the negative regulation of Toll like receptor (TLR) signalling, and inflammatory cytokines [17].…”

microRNA-27a rs895819 is associated with obesity in HIV infected preeclamptic Black South African women on HAART

“…Genetic polymorphisms in miRNA have been shown to affect miRNA expression, maturation or mRNA recognition and may represent an important risk determinant of disease susceptibility [18]. The miR-27a single nucleotide polymorphism (SNP), rs895819 is located in the terminal loop of pre-miR-27a [19].…”