Novel Variants in the IL-38 Gene Shape Genetic Susceptibility in Systemic Lupus Erythematosus

Available evidence has shown a genetic association with systemic lupus erythematosus (SLE) pathogenesis. Interleukin-38 (IL-38) has been found to correlate with SLE development. However, whether IL-38 gene polymorphisms relate to SLE risk needs clarification.

A total of 390 age- and sex-matched SLE patients and 390 healthy controls were recruited from the Affiliated Hospital of Southwest Medical University. Blood samples were collected from all the participants. Clinical and laboratory characteristics were collected and evaluated. DNA samples were extracted, and their quality was assessed. Six IL-38 gene polymorphisms (rs3811058, rs3811051, rs3811050, rs28992498, rs28992497, and rs7599662) were screened. Genotyping was performed using KASP methods.

All the six polymorphisms conformed to the Hardy-Weinberg's expectation test. The frequencies of genotypes TT and TT + TC of rs3811058 were lower in SLE patients compared to healthy controls (OR = 1.518, OR = 1.461). Similarly, for rs7599662, the frequencies of genotypes TT, TT + TC, and allele T were lower in SLE patients than in healthy controls (OR = 2.052, OR = 2.494, OR = 1.645). Conversely, the frequency of genotype TC in SLE patients was higher than that in healthy controls (OR = 1.972). Subgroup analysis showed that these gene polymorphisms were associated with various clinical and laboratory features in SLE patients. Notably, the TT + TC genotype of rs3811058 was negatively associated with lupus headache and pyuria. Furthermore, patients with the TT + TC genotype of rs3811058 had higher IgA levels, whereas SLE patients with the CC + CA genotype of rs28992498 showed lower RF and IgG expression.

IL-38 gene polymorphisms (rs3811058 and rs7599662) are associated with SLE susceptibility, and are partially associated with clinical and laboratory features.