Association Between Gamma-Glutamyl Transferase, Total Bilirubin and Systemic Lupus Erythematosus in Chinese Women

Abstract

Background: Systemic lupus erythematosus (SLE) affects many organs and systems of the human organism, at present, its specific pathogenesis is not completely clear, but inflammation is considered to be an important factor involved in the pathogenesis and progression of SLE. Gamma-glutamyl transpeptidase (GGT) and total bilirubin (TBIL) have different effects on inflammation: GGT has pro-inflammatory effects, on the contrary, TBIL has anti-inflammatory effects. Study has found that GGT and TBIL play opposite roles in metabolic diseases. However, the roles of them in SLE are unknown. Meanwhile, the relationship between GGT and SLE also remains unexplored.

Method: We recruited 341 SLE patients and 332 healthy individuals in Liaocheng People's Hospital from August 2018 to May 2019. We diagnosed SLE using 2019 revised American College of Rheumatology (ACR) SLE criteria, and modeled the study outcomes using logistic regression to explore the respective relationship between GGT, TBIL and SLE. We also analyzed the interaction of GGT and TBIL in the progression of SLE.

Results: We found that the levels of CRP, IL-6 and TNF-α in the aggravated group were significantly higher than those in the unaggravated group, the levels of C3 and C4 in the aggravated group were significantly lower than those in the unaggravated group. According to Spearman correlation analysis, GGT is proportional to CRP (r_s=0.417) and IL-6 (r_s=0.412), inversely proportional to C3 (r_s=-0.177) and C4 (r_s=0.-132). TBIL was inversely proportional to CRP (r_s=-0.328) and TNF(r_s=-0.360), and positively proportional to C3 (r_s=0.174) and C4 (r_s=0.172). In the fully adjusted model, compared to the lowest quartile, the highest quartile of GGT exhibited a positive association with the risk of SLE aggravation (OR=2.99, 95% CI: 1.42-6.31, P<0.001). At the same time, compared to the highest quartile, the quartile lowest of TBIL exhibited a positive association with the risk of SLE aggravation (OR=2.66, 95% CI: 1.27-5.59, P<0.001) in the fully adjusted model. Through interaction analysis, we found that women with high GGT levels had an increased risk of SLE aggravation when they had a low level of TBIL (OR=3.68, 95% CI: 1.51-9.01, for women with Q1 TBIL and Q4 GGT compared to women with Q2-Q4 TBIL and Q1-Q3 GGT, P for interaction <0.001), the combined AUC value (AUC_COMBINED=0.711) of high GGT level and TBIL were higher than their respective values (AUC_GGT=0.612, AUC_TBIL=0.614).

Conclusion: We found that the effects of GGT and TBIL in the progression of SLE are opposite. High GGT level might be a risk factor for SLE aggravation, as GGT levels increased, so did the risk of SLE aggravation. At the same time, we found that low TBIL level might be a risk factor for SLE aggravation. Moreover, high GGT level and low TBIL level had a subadditive effect on the increased risk of SLE aggravation.

Keywords: case-control study; diagnostic marker; female population; gamma-glutamyl transferase; systemic lupus erythematosus; total bilirubin.

Figure 1

Association of TBIL, GGT and aggravation of SLE in patients. Model 1: unadjusted. Model 2: adjusted for age, BMI, smoking status, alcohol consumption and estrogen level. Model 3: adjusted for age, BMI, smoking status, alcohol consumption, estrogen level, ALT, AST, SUA, CRP, IL-2, IL-4, IL-6, IL-10, TNF-α, hypertension, hyperlipidemia and diabetes mellitus. GGT: Q1, quartile 1 (n=89): ≤14 U/L; Q2, quartile 2 (n=88): 15-20 U/L; Q3, quartile 3 (n=82): 21-31 U/L; Q4, quartile 4 (n=82): >31 U/L. TBIL: Q1, quartile 1 (n=90): ≤8.3 mg/L; Q2, quartile 2 (n=83): 8.4-10.9 mg/L; Q3, quartile 3 (n=84): 11.0-13.8 mg/L; Q4, quartile 4 (n=84): >13.8 mg/L.

Figure 2

Interaction between TBIL and GGT in aggravation of SLE in patients. Model 1: unadjusted. Model 2: adjusted for age, BMI, smoking status, alcohol consumption and estrogen level. Model 3: adjusted for age, BMI, smoking status, alcohol consumption, estrogen level, ALT, AST, SUA, CRP, IL-2, IL-4, IL-6, IL-10, TNF-α, hypertension, hyperlipidemia and diabetes mellitus.

Figure 3

ROC curve of TBIL, GGT and the combined effect in development of SLE.