Characterization of a cyclooxygenase-2-765G→C promoter polymorphism in human neural cells

Direct sequencing of the human cyclooxygenase-2 gene promoter revealed a common single nucleoticle substitution, cyclooxygenase-2-765G -> C, in 24.5% of the populations analyzed. This change introduced a 20 base pair polypyrimicline/polypurine element and a partial recognition feature for RXR alpha, the 9-cis retinoic acid receptor, into the polymorphic promoter. Cyclooxygenase-2-765G -> C constructs, when transfected into human neural cells, exhibited a 1.4-fold higher level of basal expression, while the proinflammatory factors interleukin-1 beta and 9-cis retinoic acid synergistically induced polymorphic promoter activity 2.4-fold over wild type. These results suggest that under specific conditions of cellular stress, a common variation in cyclooxygenase-2 promoter structure may enhance cyclooxygenase-2 transcription, and this may contribute to the proliferation of an inflammatory response in brain cells. (c) 2005 Lippincott Williams & Wilkins.