rs6445975

This meta-analysis of 13 studies examined associations between PXK and TYK2 polymorphisms and systemic lupus erythematosus (SLE) susceptibility. The rs6445975 polymorphism in PXK was significantly associated with increased SLE risk in Europeans (OR = 1.198, P = 3.4E-07) but not Asians. The rs2304256 polymorphism in TYK2 showed a protective association with SLE in Europeans (OR = 0.700, P = 1.3E-04) but not Asians. Other TYK2 variants (rs12720270, rs280519, rs12720356) showed no significant associations.

This study examined the association between PXK rs6445975 and systemic lupus erythematosus (SLE) in 527 Korean SLE patients and 517 controls. Unlike the original Caucasian GWAS which found significant association (OR=1.25, p=7.1×10⁻⁹), no significant association was detected in Koreans (OR=1.06, p=0.57). However, subphenotype analysis revealed positive associations with photosensitivity (p=0.02) and anti-Sm antibody production (p=0.04), suggesting PXK may have population-specific genetic effects on SLE.

A meta-analysis of 4,107 type 2 diabetes cases and 5,187 controls from three GWA studies found no evidence that common variants altering circulating inflammatory protein levels (IL-18, IL-6R, CRP, IL1RN, PAI1, MIF) or variants predisposing to autoimmune diseases (type 1 diabetes, rheumatoid arthritis, Crohn's disease, celiac disease, multiple sclerosis, SLE) are associated with type 2 diabetes risk. For example, rs2250417 in IL18 showed OR=1.00 (95% CI 0.99-1.03) versus the expected OR of ~1.15 if inflammation were causal, suggesting inflammatory markers are likely secondary rather than causative in type 2 diabetes.