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Multiple lines of evidence have shown that systemic lupus erythematosus (SLE) is attributable to both genetic and environmental factors. The product of GRB2 is a key factor in the activation of B cells and has been reported to be significantly associated with SLE in European populations. In the study, we aimed to investigate the relationship between GRB2 and SLE. A total of 1,710 Han Chinese women comprising 567 SLE patients and 1,143 controls were recruited to genotype 20 selected tagging SNPs. We tested the potential association between 13 clinical variables of SLE and the significant polymorphisms related to SLE. The eQTL data were extracted from the GTEx database to examine the functional consequences of the targeted SNPs. A significant association signal was identified between rs36023980 and SLE in both genotypic and allelic analyses (OR = 0.61, P = 0.0003). Complement inhibition was shown to be significantly associated with the genotypes of SNP rs36023980 in SLE patients (P genotype  = 0.003). Further stratification analyses showed that the genetic association signal of SNP rs36023980 on SLE could only be identified in cases with complement inhibition. SNP rs36023980 was also identified to be significantly associated with the expression of GRB2 in whole blood and sun-exposed skin. In conclusion, our findings confirm the results from the previous GWAS and are the first to report the association of GRB2 with SLE in Han Chinese population.

Objective: The aims of this study were to investigate microRNA (miRNA) expression profiles in the periurethral vaginal wall tissues of postmenopausal women with and without stress urinary incontinence (SUI) and to explore the putative target genes associated with SUI via miRNA-messenger RNA (mRNA) pair prediction., Methods: Periurethral vaginal wall tissues of postmenopausal women with SUI (n = 13) and matched continent postmenopausal women (n = 13) were collected during transvaginal surgical operation. Total RNAs were extracted and miRNAs were profiled by TaqMan Array Human MicroRNA assays in three case-control pairs. TargetScanS, PicTar, and miRanda were used to obtain the putative miRNA-mRNA pairs based on sequence data, and three pairs were predicated. The relative expression levels of miRNAs in predicated miRNA-mRNA pairs were quantified in 10 other case-control pairs by real-time polymerase chain reaction. The expression levels of mRNAs and corresponding proteins were estimated via real-time polymerase chain reaction and Western blot analysis., Results: Twelve miRNAs were identified to be differentially expressed between two groups: the significantly up-regulated let-7a, miR-101#, miR-125b-2#, miR-190b, and miR-892b, and the down-regulated miR-124, miR-330-3p, miR-485-3p, miR-517b, miR-523, miR-589, and miR-93#. Moreover, three miRNA-mRNA pairs of interest were established via computational algorithms: miR-124 and growth factor receptor-bound protein 2; miR-330-3p and bicaudal D homolog 2; and miR-93# and signal transducer and activator of transcription 3. The expression levels of the three miRNAs were quantified, and a reduction in SUI was revealed. On the other hand, increased expression levels of predicated mRNAs and their protein products were detected., Conclusions: This study reports the differential expression of 12 miRNAs in SUI and predicates three miRNA-mRNA pairs. Interestingly, all three predicated target genes are associated with neurodegenerative conditions, indicating the potential significance of neurodegenerative mechanisms in the etiology of SUI.