Association between COX-2 and 15-PGDH polymorphisms and SLE susceptibility.

Area of Science:

• Immunogenetics
• Rheumatology
• Molecular Biology

Background:

• Systemic lupus erythematosus (SLE) is a chronic autoimmune disease.
• Prostaglandins E2 (PGE2), synthesized by cyclo-oxygenase 2 (COX-2), play a role in autoimmune disease etiology.
• PGE2 levels are regulated by COX-2 and 15-hydroxyprostaglandin dehydrogenase (15-PGDH).

Purpose of the Study:

• To investigate the association between genotypic polymorphisms in COX-2 and 15-PGDH and SLE.
• To determine the role of specific polymorphisms (COX-2 rs2745557 and 15-PGDH rs8752) in SLE susceptibility.

Main Methods:

• Genotyping of 160 SLE patients and 160 healthy controls using polymerase chain reaction - restriction fragments length polymorphism.
• Analysis of COX-2 rs2745557 G/A and 15-PGDH rs8752 G/A polymorphisms.

Main Results:

• No significant association was found for COX-2 rs2745557 polymorphism with SLE, though a dominant model showed marginal significance (P=0.048).
• The 15-PGDH rs8752 GA genotype was significantly associated with a 4.5-fold increased risk of SLE (P=0.0001).
• The 15-PGDH A allele was more frequent in SLE patients, increasing SLE development by 1.4-fold (P=0.018).

Conclusions:

• The dominant model of COX-2 rs2745557 polymorphism demonstrates protective effects against SLE.
• The 15-PGDH rs8752 polymorphism is identified as a risk factor for SLE development.