Cyclo-oxygenase-2 -765G > C promoter variants are associated with lower carotid plaque echogenicity in Japanese.
OBJECTIVE
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.
Furukado
Shigetaka
S
Department of Neurology, Stroke Division, Osaka University Graduate School of Medicine, Osaka, Japan.
Sakaguchi
Manabu
M
Yamagami
Hiroshi
H
Yagita
Yoshiki
Y
Hoshi
Taku
T
Abe
Yuko
Y
Hougaku
Hidetaka
H
Hori
Masatsugu
M
Sakoda
Saburo
S
Kitagawa
Kazuo
K
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000368:Aged; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000453:epidemiology; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging* / Q000453:epidemiology*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D048909:Diabetes Complications; D050171:Dyslipidemias / Q000000981:diagnostic imaging / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D014463:Ultrasonography
D015121:6-Ketoprostaglandin F1 alpha; D004247:DNA; D051546:Cyclooxygenase 2