Associations of RPEL1 and miR-1307 gene polymorphisms with disease susceptibility, glucocorticoid efficacy, anxiety, depression, and health-related quality of life in Chinese systemic lupus erythematosus patients.

OBJECTIVE: Our present study intended to examine the associations of RPEL1 and miR-1307 gene polymorphisms (rs4917385 and rs7911488) with susceptibility, glucocorticoids (GCs) efficacy, anxiety, depression, and health-related quality of life (HRQoL) in Chinese systemic lupus erythematosus (SLE) patients. METHODS: Initially, 1000 participants (500 SLE cases and 500 controls) were recruited for the case-control study. Then, 429 cases who received GCs were followed through 12 weeks to explore GCs efficacy, depression, anxiety, and HRQoL. We selected the iMLDR technique for genotyping: RPEL1: rs4917385 (G/T) and miR-1307: rs7911488 (A/G). RESULTS: The minor G allele of rs7911488 reduced the risk of SLE (p = .024). Four haplotypes consisting of rs4917385 and rs7911488 were associated with SLE susceptibility (p < .025). Both rs4917385 and rs7911488 were associated with anxiety symptoms and physical function (PF) in SLE patients (p < .025). The rs4917385 was associated with depression and its improvement. No statistical significance was found between RPEL1 and miR-1307 gene polymorphisms with GCs efficacy. Meanwhile, additive interaction analysis showed a significant association between RPEL1 and miR-1307 gene polymorphisms with tea consumption in anxiety. CONCLUSION: RPEL1 and miR-1307 gene polymorphisms (rs4917385 and rs7911488) might be related to SLE susceptibility in Chinese population. Additionally, the two polymorphisms were possibly associated with depression, anxiety, and HRQoL in Chinese SLE population.

Mitochondrial DNA genetic variants are associated with systemic lupus erythematosus susceptibility, glucocorticoids efficacy and prognosis.

OBJECTIVE: To investigate the associations of mitochondrial DNA (mtDNA) genetic variants with SLE susceptibility, glucocorticoid (GC) efficacy and prognosis. METHODS: Our study was done in two stages. First, we performed whole mitochondrial genome sequencing in 100 patients and 100 controls to initially screen potential mtDNA variants associated with disease and GC efficacy. Then, we validated the results in an independent set of samples. In total, 605 SLE patients and 604 normal controls were included in our two-stage study. A two-stage efficacy study was conducted in 512 patients treated with GCs for 12 weeks. We also explored the association between mtDNA variants and SLE prognosis. RESULTS: In the combined sample, four mtDNA variants (A4833G, T5108C, G14569A, CA514-515-) were associated with SLE susceptibility (all PBH < 0.05). We confirmed that T16362C was related to efficacy of GCs (PBH = 0.014). Significant associations were detected between T16362C and T16519C and the efficacy of GCs in females with SLE (PBH < 0.05). In the prognosis study, variants A4833G (PBH = 0.003) and G14569A (PBH = 9.744 × 10-4) substantially increased SLE relapse risk. Female patients harbouring variants T5108C and T16362C were more prone to relapse (PBH < 0.05). Haplotype analysis showed that haplogroup G was linked with SLE susceptibility (PBH = 0.001) and prognosis (PBH = 0.013). Moreover, mtDNA variant-environment interactions were observed. CONCLUSION: We identified novel mtDNA genetic variants that were associated with SLE susceptibility, GC efficacy, and prognosis. Interactions between mtDNA variants and environmental factors were related to SLE risk and GC efficacy. Our findings provide important information for future understanding of the occurrence and development of SLE.

Aromatic hydrocarbon receptor provides a link between smoking and rheumatoid arthritis in peripheral blood mononuclear cells.

OBJECTIVES: Epidemiology shows that smoking plays a central role in rheumatoid arthritis (RA). The aim of this study was to evaluate the potential relationship between smoking, aromatic hydrocarbon receptor (AHR) and RA susceptibility. METHODS: We performed a hospital-based, case-control study of patients with RA and healthy controls. Expressions of AHR, cytochrome P4501A1(CYP1A1), aromatic hydrocarbon receptor repressor (AHRR) genes were assessed in peripheral blood mononuclear cells (PBMCs) and cultured cells using real-time PCR. The response of PBMCs to the AHR agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and cigarette smoke extract (CSE) were cultured in vitro. RESULTS: AHR and its downstream gene expressions were demonstrated in smoking rheumatoid PBMCs and non-smoking patients with significantly higher expression in smoking patients. The observation was consistent with the sensitivity of RA PBMCs to TCDD and CSE stimulation demonstrated in vitro. CONCLUSIONS: Our study shows that smoking may be involved in the pathogenesis of RA by the AHR pathway.