The Impacts of the Clinical and Genetic Factors on Chronic Damage in Caucasian Systemic Lupus Erythematosus Patients

Abstract

Objective: The purpose of this study was to determine the distribution of organ damage in a cohort of systemic lupus erythematosus (SLE) patients and to evaluate the roles of clinical and genetic factors in determining the development of chronic damage. Methods: Organ damage was assessed by the SLICC Damage Index (SDI). We analyzed a panel of 17 single-nucleotide polymorphism (SNPs) of genes already associated with SLE, and we performed a phenotype−genotype correlation analysis by evaluating specific domains of the SDI. Results: Among 175 Caucasian SLE patients, 105 (60%) exhibited damage (SDI ≥1), with a median value of 1.0 (IQR 3.0). The musculoskeletal (26.2%), neuropsychiatric (24.6%) and ocular domains (20.6%) were involved most frequently. The presence of damage was associated with higher age, longer disease duration, neuropsychiatric (NP) manifestations, anti-phospholipid syndrome and the positivity of anti-dsDNA. Concerning therapies, cyclophosphamide, mycophenolate mofetil and glucocorticoids were associated with the development of damage. The genotype−phenotype correlation analysis showed an association between renal damage, identified in 6.9% of patients, and rs2205960 of TNFSF4 (p = 0.001; OR 17.0). This SNP was significantly associated with end-stage renal disease (p = 0.018, OR 9.68) and estimated GFR < 50% (p = 0.025, OR 1.06). The rs1463335 of MIR1279 gene was associated with the development of NP damage (p = 0.029; OR 2.783). The multivariate logistic regression analysis confirmed the associations between TNFSF4 rs2205960 SNP and renal damage (p = 0.027, B = 2.47) and between NP damage and rs1463335 of MIR1279 gene (p = 0.014, B = 1.29). Conclusions: Our study could provide new insights into the role of genetic background in the development of renal and NP damage.

Keywords: MIR1279; TNFSF4; chronic damage; genetics; polymorphisms; systemic lupus erythematosus.

Figure 1

The distribution of SDIs in our SLE cohort [please read clockwise starting from the largest group with SDI = 0].

Figure 2

The associations between renal damage and rs2205960 of TNFSF4 [p = 0.001]. In addition, this SNP was significantly associated with the development of two specific items on the SDI renal domain: estimated glomerular filtration rate (GFR) <50% and end-stage renal disease (ESRD) (p = 0.025, p = 0.018 respectively).

Figure 3

(A): Associations between rs1463335 of MIR1279 and the development of neuropsychiatric damage (p = 0.029). (B): rs9469003 of HCP5 locus was significantly associated with the GC-SDI domain (p = 0.028).