Neprilysin-like2之基因多型性及阿茲海默症之關聯

Objective: The deposition of amyloid β(Aβ) plays a crucial role in the pathogenesis of Alzheimers disease (AD). Beta-site APP cleaving enzyme (BACE) is the rate-limiting enzyme in the A$ formation. Neprilysin (NEP), on the other hand, is the enzyme responsible to degrade the Aβ. There are many pieces of evidence implicating genetic factors are attributable to the susceptibility of AD. Neprlysin-like 2 or membrane metallo-endopeptidase-like 2 (MMEL2) is a candidate of human homolog of murine neprilysin 2 (NEP2). NEP2 and NEP complementarily distribute in the brain and recombinant NEP2 was shown to cleave the same neuropeptides as NEP. MMEL2 might be another degradation enzyme of A. Methods: We searched the MMEL2 polymorphisms in exon 1, which encodes the transmembrane domain, by SSCP followed by sequencing and PCR-RFLP A total of 107 AD patients along with 118 controls were recruited in this study. Results: Two polymorphisms at -7A/C and 15C/T were found and then two haplotypes were identifed. The haplotype frequencies of the haplotypes were 0.388 for -7A15C (haplotype 1) and 0.612 for -7C15T (haplotype 2) in AD. In controls, the haplotype 1 and haplotype 2 frequencies were 0.415 and 0.585, respectively. Conclusion: No significant association of this polymorphism with the occurrence of AD can be established.