Association of microRNA-34a rs2666433 (A/G) Variant with Systemic Lupus Erythematosus in Female Patients: A Case-Control Study.

Several microRNAs (miRNAs) are associated with autoimmune disease susceptibility and phenotype, including systemic lupus erythematosus (SLE). We aimed to explore for the first time the role of the miRNA-34a gene (MIR34A) rs2666433A > G variant in SLE risk and severity. A total of 163 adult patients with SLE and matched controls were recruited. Real-Time allelic discrimination PCR was applied for genotyping. Correlation with disease activity and clinic-laboratory data was done. The rs2666433 variant conferred protection against SLE development under heterozygous [A/G vs. G/G; OR = 0.57, 95%CI = 0.34-0.95], homozygous [A/A vs. G/G; OR = 0.52, 95%CI = 0.29-0.94], dominant [A/G + A/A vs. GG; OR = 0.55, 95%CI = 0.35-0.88], and log-additive [OR = 0.71, 95%CI = 0.53-0.95] models. Data stratification by sex revealed a significant association with SLE development in female participants under heterozygous/homozygous models (-interaction = 0.004). There was no clear demarcation between SLE patients carrying different genotypes regarding the disease activity index or patients stratified according to lupus nephritis. Enrichment analysis confirmed the implication of MIR34A in the SLE pathway by targeting several genes related to SLE etiopathology. In conclusion, although the MIR34A rs2666433 variant conferred protection against developing SLE disease in the study population, it showed no association with disease activity. Replication studies in other populations are warranted.