CAJ | 학술논문

目的探讨水通道蛋白4(AQP4)启动子区基因多态性与我国南方多发性硬化(MS)、视神经脊髓炎(NMO)患者血清抗AQP4抗体水平及遗传易患性的关系.方法收集18例NMO、38例MS、13例复发性脊髓炎(RM)、6例复发性视神经炎(RON)患者及39名对照,PCR扩增AQP4外显子0及外显子1启动子基因(即AQP4-promoter0和AQP4-promoter 1),并行DNA测序.结果共发现14个AQP4-promoter0及6个AQP4-promoter 1基因多态性位点.血清抗AQP4抗体阳性患者AQP4-promoter 0中-1003 bp多态性位点(A突变为G)发生率比血清抗AQP4抗体阴性患者(13/18与20/45,P=0.046)及对照组(13/18与10/39,P=0.001)高,差异有统计学意义.血清抗AQP4抗体阳性患者及血清抗AQP4抗体阴性患者AQP4-promoter 1中- 401 bp与-400 bp之间多态性位点(插入1个C)发生率均比对照组高(5/16与0/28,P=0.008; 8/38与0/28,P=0.027),差异有统计学意义.NMO及MS患者-1003bp多态性位点及-401 bp与-400 bp之间多态性位点发生率均比对照组高,差异有统计学意义(NMO:11/18与10/39,P=0.010;4/15与0/28,P=0.020；MS:19/38与10/39,P=0.027;8/34与0/28,P=0.018).结论 AQP4启动子区基因存在多态性位点,且与NMO、MS易患性有一定的关系；AQP4外显子0启动子中- 1003 bp多态性位点可能与血清抗AQP4抗体的出现有关.
목적 탐토수통도단백4(AQP4)계동자구기인다태성여아국남방다발성경화(MS)、시신경척수염(NMO)환자혈청항AQP4항체수평급유전역환성적관계.방법 수집18례NMO、38례MS、13례복발성척수염(RM)、6례복발성시신경염(RON)환자급39명대조,PCR확증AQP4외현자0급외현자1계동자기인(즉AQP4-promoter0화AQP4-promoter 1),병행DNA측서.결과 공발현14개AQP4-promoter0급6개AQP4-promoter 1기인다태성위점.혈청항AQP4항체양성환자AQP4-promoter 0중-1003 bp다태성위점(A돌변위G)발생솔비혈청항AQP4항체음성환자(13/18여20/45,P=0.046)급대조조(13/18여10/39,P=0.001)고,차이유통계학의의.혈청항AQP4항체양성환자급혈청항AQP4항체음성환자AQP4-promoter 1중- 401 bp여-400 bp지간다태성위점(삽입1개C)발생솔균비대조조고(5/16여0/28,P=0.008; 8/38여0/28,P=0.027),차이유통계학의의.NMO급MS환자-1003bp다태성위점급-401 bp여-400 bp지간다태성위점발생솔균비대조조고,차이유통계학의의(NMO:11/18여10/39,P=0.010;4/15여0/28,P=0.020；MS:19/38여10/39,P=0.027;8/34여0/28,P=0.018).결론 AQP4계동자구기인존재다태성위점,차여NMO、MS역환성유일정적관계；AQP4외현자0계동자중- 1003 bp다태성위점가능여혈청항AQP4항체적출현유관.
Objective To investigate the associations of aquaporin-4 (AQP4) promoter polymorphisms with anti-AQP4 antibody and genetic susceptibility to multiple sclerosis (MS) and neuromyelitis optica (NMO) in Southern Chinese population.Methods The polymorphisms of AQP4promoter 0 and 1 were analyzed by PCR and DNA sequencing in 18 NMO,38 MS,13 recurrent myelitis (RM),6 recurrent optic neuritis (RON) patients and 39 healthy controls. Results Fourteen polymorphism loci were observed in AQP4-promoter 0,while 6 ones were observed in AQP4-promoter 1.Among them,the incidence rate of polymorphism at position - 1003 bp (A-G) of AQP4-promoter 0 in anti-AQP4 antibody-positive patients was significantly higher than that in anti-AQP4 antibody-negative patients and controls (former:13/18 vs 20/45,P =0.046; latter:13/18 vs 10/39,P =0.001 ).The incidence rates of polymorphism at position between -401 bp and -400 bp ( C inserted) of AQP4-promoter 1 in anti-AQP4 antibody-positive and -negative patients were significantly higher than that in controls( former:5/16 vs 0/28,P =0.008; latter:8/38 vs 0/28,P =0.027 ). The incidence rates of polymorphism at position - 1003 bp (A-G) of AQP4-promoter 0 and position between -401 bp and -400 bp ( C inserted)of AQP4-promoter 1 in patients with NMO and MS were significantly higher than that in controls( NMO:11/18 vs 10/39,P =0.010;4/15 vs 0/28,P =0.020; MS:19/38 vs 10/39,P =0.027;8/34 vs 0/28,P =0.018).Conclusions Polymorphisms loci were observed in AQP4-promoter 0 and AQP4-promoter 1,which may have an influence on the susceptibility to MS and NMO.Polymorphism at position - 1003 bp ( A-G) of AQP4-promoter 0 may be related to the emergence of anti-AQP4 antibody in patients with NMO and MS.