Immunogenetic Relationship of HLA-G 14 bp Insertion/Deletion Polymorphism and Toll-Like Receptor 9 with Systemic Lupus Erythematosus in Egyptian Patients: A Case-Control Study

Abstract

Introduction The level of expression of the immunoregulatory human leukocyte antigen-G (HLA-G) has been suggested to play a role in the immunopathogenesis of systemic lupus erythematosus (SLE). A 14 bp insertion/deletion (ins/del) polymorphism in the 3ˊuntranslated region of HLA-G gene may influence the level of expression. The role of Toll-like receptor 9 (TLR9) in the pathogenesis of SLE has been highlighted. Data among Egyptian patients are quite limited. Purpose To detect the association of HLA-G 14 bp ins/del gene polymorphism with the susceptibility to SLE and to correlate TLR9 serum level with disease activity among Egyptian patients. Patients and Methods A case-control study that included 102 SLE female patients and 102 healthy matched volunteers as controls was carried out. Disease activity in patients was determined using the modified Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). HLA-G 14 bp ins/del genotype was detected by polymerase chain reaction (PCR). TLR9 serum level was estimated using enzyme-linked immunosorbent assay (ELISA) technique. Results The ins/ins genotype was significantly increased among SLE patients compared to healthy subjects (58.8% vs 9.8%; odds ratio [OR] = 11.79, P < 0.001). The 14 bp ins allele was significantly more frequent in SLE patients than in healthy subjects (65.7% vs 27.9%, respectively) and significantly associated with an increased risk of SLE (OR 4.94, P < 0.001). The mean TLR9 serum level showed a significant increase in SLE patients compared to healthy subjects (397.04±137.86 vs 195.22±45.14 ng/L, p < 0.001) and was significantly associated with disease activity as well as to patients’ HLA-G genotypes (p < 0.001). Conclusion Among Egyptian population, HLA-G 14 bp ins/ins homozygous genotype and ins allele may constitute a potential risk for SLE susceptibility, while TLR9 serum level is significantly associated with disease activity.

Association study of 3-UTR haplotype of HLA-G gene with Lupus

“…While the majority of reports, including the current study, suggest an association between the Ins allele and Ins/Ins genotype with SLE, inconsistent results across some studies may be attributed to differences in study populations, sample sizes, and other factors. Further research is needed to fully understand the role of this polymorphism in the development and progression of SLE and to determine whether it could be a potential target for future therapies [13][14][15][16][17].…”

“…These ndings suggest that the association between the rs1710 polymorphism and SLE susceptibility may vary by population, highlighting the importance of considering population-speci c genetic differences in SLE susceptibility. Further studies may provide greater clarity on the potential implications of this polymorphism in the development of new diagnostic or therapeutic approaches for SLE [16][17][18][19].…”

“…The inconsistent results across studies may be attributed to differences in study populations, sample sizes, and other factors, and more rigorous studies with standardized genotyping methods and larger sample sizes are needed to better understand the potential role of these genetic variants in SLE susceptibility. It is also worth noting that the 3' UTR of the HLA-G gene is involved in post-transcriptional regulation of HLA-G expression, and genetic variants in these regions may affect HLA-G expression levels, which could potentially in uence SLE susceptibility [15][16][17][18][19][20][21][22].…”

“…The rs371194629 polymorphism affects HLA-G mRNA expression and has been studied for its association with systemic lupus erythematosus (SLE), an autoimmune disease. However, the results of these studies have been inconsistent, with some nding a signi cant association and others nding no signi cant association [12][13][14][15][16][17].…”