LAUSR

OBJECTIVE Cyclooxygenase (COX)-2, an inducible isoform of the major rate-limiting enzymes that regulate the production of prostaglandins is associated with injury, inflammation and proliferation. We sought to examine whether plasma COX-2 levels and its genetic variants is associated with salt sensitivity, BP changes and/or hypertension in humans. METHODS Eighty participants (aged 18-65 years) were maintained sequentially either on a usual diet for 3 days, a low-salt diet (3.0 g) for 7 days, and a high-salt diet (18.0 g) for an additional 7 days. In addition, we studied participants of the original Baoji Salt-Sensitive Study, recruited from 124 families from seven Chinese villages in 2004 who received the same salt intake intervention, and evaluated them for the development of hypertension. RESULTS Plasma COX-2 levels were significantly decreased with reduction of salt intake from the usual to a low-salt diet and decreased further when converting from the low-salt to the high-salt diet. SNPs rs12042763 in the COX-2 gene was significantly associated with SBP responses to both low-salt and high-salt diet. SNPs rs689466 and rs12042763 were significantly associated with longitudinal changes in BPs. In addition, several COX-2 SNPs were significantly associated with incident hypertension over an 8-year follow-up. Gene-based analyses also supported the overall association of COX-2 with longitudinal changes in SBP and hypertension incidence. CONCLUSION This study shows that dietary salt intake affects plasma COX-2 levels and that COX-2 may play a role in salt sensitivity, BP progression and development of hypertension in the Chinese populations studied.