Neprilysin-like 2 (MMEL2) Polymorphisms in Alzheimer's Disease

Neprilysin-like2之基因多型性及阿茲海默症之關聯

劉興政(Hsing-Cheng Liu) ； 呂思潔(Sy-Jye Leu) ； 張建國(Jan-Gowth Chang) ； 宋成銘(Shing-Ming Sung) ； 許偉貞(Wei-Chen Hsu) ； 李龍雄(Long-Shyong Lee) ； 胡朝榮(Chaur-Jong Hu)

《北市醫學雜誌》 1卷4期 (2004/10) Pp. 418-425

https://doi.org/10.6200/TCMJ.2004.1.4.05

摘要

乙型類澱粉（amyloid 戶的堆積在阿茲海默症的病因扮演重要角色。乙型位置類澱粉前驅蛋白酵素（Beta-Site APP cleaving enzyme）是乙型類澱粉形成之決定步驟，而 Neprilvsin（NEP）則是代謝乙型類澱粉的重要酵素；許多證據指出基因因子參與阿茲海默症之發病。Neprilvsinl-ke2或membrane metallo-endopeptidase-like2（MMEL2）是人類相似於老鼠 neprilysin2（NEP2）之基因，NEP2與NEP具有類似之神經牲肽代謝功能，因此吾人推斷MMEL2基因應可能為阿茲海默症之候選基因。吾人先以單股結構多型性（SSCP）尋找 MMEL2基因第一外子（exon l）之基因多型性，接著以基因定序確定吾人之發現：MMEL2基因第一外子有二個基因多型性，分別是-7A / C及15C / T，但二者存在於二個對偶型（haplotypes）：-7A15C（allele l）與-7C15T（allele2）。最後107位阿玆海默症病人與118位非阿茲海默症老人接受MMELZ基因型之研究。本研究發現阿茲海默症病人－7A15C（allele 1）頻率為0.388，-7C15T（allele 2）為0.612；非阿茲海默症老人allele 1及allele 2則分別為0.415與0.585，二組並無差異。

關鍵字

Neprilysin ； 阿茲海默症 ； 乙型類澱粉 ； metallo-endopeptidase-like2

並列摘要

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.

並列關鍵字

Alzheimer's disease ； amyloid β ； metallo-endopeptidase-like2 ； neprilysin