Association of plasma cyclooxygenase-2 levels and genetic polymorphisms with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults

Abstract

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.

Associations of Serum Uromodulin and Its Genetic Variants With Blood Pressure and Hypertension in Chinese Adults

“…In addition, we used the truncated product method (TPM), which combines P values from each SNP association analysis, to evaluate the overall associations of UMOD gene with longitudinal BP changes and the incidence of hypertension ( 19 , 24 , 35 ). Gene-based analysis is a method that can evaluate the association between a trait and a candidate gene, and is performed with R software (version 3.0.1; http://www.r-project.org ).…”

“…Assembled from April to November 2004, the Baoji Salt-Sensitive Study cohort consists of 514 adults from 124 families in seven villages in Baoji, Shaanxi, China. The detailed design of this study has been published previously (19)(20)(21)(22)(23)(24). To explore the associations of UMOD genetic variations with longitudinal BP changes and hypertension incidence, we followed up this cohort in 2009 and 2012.…”

“…Genomic DNA was isolated and purified from the whole blood samples by the GoldMag-Mini kits (GoldMag Co. Ltd. Xian, China). All the genotyping experiments were completed by CapitalBio (CapitalBio Corp, Beijing, China) as previously described (19)(20)(21)(22)24).…”

Associations of corin genetic polymorphisms with salt sensitivity, blood pressure changes, and hypertension incidence in Chinese adults

“…Therefore, as described previously, we defined BP responses as follows: BP response to high salt = BP on the high‐salt diet – BP on the low‐salt diet; and BP response to the low‐salt = BP on the low‐salt diet – BP at baseline. 5 , 6 , 7 , 19 …”

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“…In addition, we used the truncated product method (TPM), which combines P values from each SNP association analysis, to evaluate the overall associations of UMOD gene with longitudinal BP changes and the incidence of hypertension (19,24,35). Genebased analysis is a method that can evaluate the association between a trait and a candidate gene, and is performed with R software (version 3.0.1; http://www.r-project.org).…”