Association between -250G/A polymorphism of the hepatic lipase gene promoter and coronary artery disease and HDL-C levels in a Southern Brazilian population.

Hepatic lipase (HL) is a glycoprotein that plays a major role in remodeling high-density lipoprotein (HDL). The effect of the -250G/A promoter polymorphism on coronary artery disease (CAD) and lipid levels was studied in 231 male CAD patients and in a population-based sample of men and women (n = 514). A sample of 140 men was chosen among those included in the population-based sample as controls for the CAD sample. In the total group of CAD patients, the frequency of the -250A allele was somewhat lower (25% in CAD patients and 32% in controls; p = 0.06), but when the control samples were compared only with the CAD(+) sample (more than 60% of luminal stenosis in at least one coronary artery or major branch segment) the -250A allele was significantly less frequent (23% in the patients vs 32% in controls; p = 0.02). A multiple logistic regression analysis showed that this association was independent of classical CAD risk factors [odds ratio (OR) = 1.79, p = 0.025]. Using multiple linear regression analyses, it has been shown that this polymorphism was a significant factor affecting HDL-C levels in men from the population-based sample (p = 0.001), an interaction between -250G/A variant and wine consumption was also detected (p = 0.001). Thus, our results show that the -250G/A polymorphism in the HL gene is associated with significant variations in HDL-C levels and CAD risk in males.

Anti-DNA antibodies cross-reacting with laminin inhibit trophoblast attachment and migration: implications for recurrent pregnancy loss in SLE patients.

PROBLEM: Systemic lupus erythematosus (SLE), an autoimmune disease, is associated with reduced fetal survival, recurrent abortions, and other pregnancy complications. Some of the autoantibodies found in SLE bind to laminins (LNs), which play an important role in the implantation of the fertilized ovum in humans. METHOD OF STUDY: To elucidate the role of these specific autoantibodies, chorionic villous explants from 6 7-week-old human placentas were established as organ cultures on laminin-1 (LN-1), collagen IV (CN-IV) or uncoated culture dishes. The cultures were then exposed to a mouse monoclonal anti-DNA/anti-LN-1 antibody, to human polyclonal lupus antibodies cross-reacting with LN-1, a function-blocking polyclonal antibody to LN-1, polyclonal antibodies to CN-IV, or IgG control. RESULTS: The explants attached to LN-1 and CN-IV, but not to uncoated culture dishes. LN-1 promoted migration of trophoblast, whereas CN-IV promoted migration of fibroblast-like cells. Trophoblast attachment and migration were abolished in a dose-dependent manner by all three antibodies to LN-1, but not by antibodies to CN-IV or IgG control. Furthermore, the effect of anti-LN antibodies was abolished by preincubating them with LN-1. CONCLUSIONS: These studies suggest that anti-DNA antibodies cross-reacting with LNs may play a role in early pregnancy failure in SLE patients by interfering with placental implantation.