Functional regulation of Alu element of human angiotensin-converting enzyme gene in neuron cells

The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) genotype and its protein activity have been widely implicated to be associated with Alzheimer's disease (AD). However, whether the insertion sequence, Alu element, in intron 16 of the human ACE gene plays a functional role remains uncertain. To investigate the influence of the I/D polymorphism on ACE promoter, we recombined the I and D form fragments with the human ACE promoter sequence before the reporter gene in pSEAP-Basic2 vector. The effect of the Alu element on regulating the transcriptional activity of ACE promoter was examined using transient transfection in SH-SY5Y cells. We found that the I form fragment upregulated the transcriptional activity of ACE promoter by approximately 70% but that the D form fragment did not. Our study first reveals that Alu sequence in human ACE gene possesses a regulatory function on the ACE promoter activity in neuron. This novel finding bridges the gap between the association of ACE I/D genotype with AD, and suggests that Alu sequence is not merely a “junk” DNA in human ACE gene.