Abstract
Systemic lupus erythematosus (SLE) involves a broad range of factors that contribute to the development of the disease and its comorbidities. Genetic predisposition influences the development of SLE, and the −675 4G/5G PAI-1 polymorphism has been associated with several pathologies with a chronic inflammatory component. Our objective was to investigate the genetic association between the −675 4G/5G PAI-1 polymorphism with SLE, its clinical manifestations, and comorbidities in a Mexican-Mestizo population. The −675 PAI-1 polymorphism was determined by PCR-RFLP in 716 subjects: 293 SLE patients and 423 control subjects. Significant associations for SLE genetic susceptibility were found in carriers of 4G/5G (OR = 2.63; CI 1.81–3.87; p < .001) and 4G/4G (OR = 2.70; CI 1.62–4.51; p < .001) genotype in comparison with the 5G/5G genotype; 4G allele carriers also presented genetic risk for SLE (OR = 1.63; CI 1.31–2.03; p < .001) compared to the 5G allele. Following a dominant genetic model, a similar association was found with the 4G allele to SLE (OR = 2.66; CI1.84–3.84; p < .001). The 4G/5G genotype was associated with shorter disease duration (p = .039), as well as lower levels of haemoglobin (p = .001) and haematocrit (p = .009); the need for prednisone treatment (p = .001), higher BMI (p = .03), presence of type 2 DM (p = .015), clinical activity (Mex-SLEDAI = 57%; p = .047), Chronicity (SLICC-ACR = 0; p = .015) and CRP levels (p = .015) were associated with 5G/5G genotypes. In conclusion, the −675 4G/5G and 4G/4G PAI-1genotypes were found as genetic risk markers of susceptibility for SLE in the Mexican-Mestizo population, and each genotype could influence the clinical manifestations and comorbidities differently in SLE.
Author contributions
J.F.M.V. conceived and organised the study and prepared the manuscript. B.U.A.M. performed the genotyping, and participated in the statistical analysis, interpreted the data, and wrote the manuscript. U.D.C.M., C.A.P.S., and I.P.R. were responsible for patient enrolment and participated in the genetic analysis. G.M.B., L.G.L., J.I.G.N., E.E.P.G., and S.L.B.A. participated in the design of the study, contributed to interpreting the data and revising successive drafts of the manuscript. All authors read and approved the final manuscript.
Disclosure statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.