The role of genetic polymorphism of fat mass and obesity-associated in lupus nephritis among patients with systemic lupus erythematosus

Background Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by diverse clinical manifestations, with lupus nephritis (LN) representing a severe form of renal involvement. The fat mass and obesity-associated (FTO) gene has been implicated in various autoimmune diseases, but its role in SLE and LN remains understudied. This study aimed to explore the association of FTO gene polymorphisms with LN in Egyptian patients with SLE. Patients and methods In this case-control study, a cohort of 240 Egyptian SLE patients (120 with LN and 120 without LN) was enrolled. PCR of two tagging single nucleotide polymorphisms of the FTO gene (rs9939609 and rs17817449) were performed and genotypes were correlated. Demographic, clinical, and laboratory data were collected, including SLE disease activity and renal function parameters. Results The study found a significant association between the FTO rs9939609 AA genotype and A allele with LN, with ORs of 3.013 and 1.712, respectively, ( P =0.004). The rs17817449 TG genotype was also linked to LN (OR: 1.863, P =0.025). Patients with the rs9939609 AA genotype had more severe renal manifestations, including higher proteinuria, serum creatinine, and systemic lupus erythematosus disease activity index scores. Conclusions FTO gene polymorphisms, specifically rs9939609 and rs17817449, are strongly linked to an increased risk of LN in SLE patients. These results underscore FTO’s role in LN pathogenesis and suggest genetic screening for these variants could help identify patients at greater risk of renal complications.