Cyclo-Oxygenase-2-765G > C Promoter Variants Are Associated with Lower Carotid Plaque Echogenicity in Japanese

Background and Purpose: Recent studies revealed that inflammation contributes to plaque instability. Cyclo-oxygenase (COX)-2 is one of the key enzymes in plaque inflammation. We examined the relation between a polymorphism in the COX-2 gene and carotid plaque echogenicity in patients with high risk of cerebrovascular disease to evaluate the involvement of COX-2 in plaque instability. Methods: The study comprised 469 individuals with carotid atherosclerotic plaques. We quantified the echogenicity of the largest plaque in each participant by integrated backscatter analysis. The -765G > C variant of the COX-2 gene was genotyped by restriction enzyme fragment length polymorphism analysis. Urinary 6-keto prostaglandin F-1 alpha levels and flow-mediated dilation were measured in 25 participants from the -765GC genotype group and 25 matched participants from the -765GG genotype group. Results: The carotid plaque echogenicity in the variant genotype group n = 44) was lower than that in the -765GG genotype group (n = 425, p = 0.017). The association remained significant when we controlled for atherosclerotic risk factors, plaque thickness and serum levels of interleukin-6 (p = 0.027). The level of urinary 6-keto prostaglandin F-1 alpha and flow-mediated dilation in the variant genotype group was significantly lower than that in the -765GG genotype group. Conclusions: The -765G > C variant of COX-2 was associated with reduced carotid plaque echogenicity in Japanese. Diminished COX-2 activity in the endothelium may contribute to plaque instability. Copyright (c) 2008 S. Karger AG, Basel