发作性睡病患者人类白细胞组织相容性抗原DQB1＊0602基因阳性率分析

Positivity analysis of human leukocyte histocompatibility antigen-DQB1＊ 0602 allele in Chinese patients with narcolepsy

目的分析发作性睡病患者人类白细胞组织相容性抗原（HLA）-DQB1＊0602基因阳性率。方法1998年8月至2011年7月在北京大学人民医院睡眠中心确诊的发作性睡病患者共1223例，根据临床表现中有无典型猝倒将其分为猝倒组（1132例）与非猝倒组（91例）2组，将其中发病年龄明确的1218例患者根据发病年龄分为早发型组（发病年龄≤15岁，1037例）和晚发型组（发病年龄〉15岁，181例）。患者均进行特异性引物．聚合酶链反应技术测定HLA-DQBls0602基因型，其中156例进行了脑脊液下丘脑分泌素（hcrt）-1的测定，并据此分为hcrt缺失组（herr．1〈138ng／L，115例）和herr正常组（herr-1≥138ng／L，41例）。另征集728名健康志愿者为对照组，对各组研究对象的HIJA-DQB1＊0602阳性情况进行调查分析。结果发作性睡病患者中男825例（67．5％），女398例（32．5％），就诊时平均年龄为（16．6±12．6）岁；对照组中男443名（60．9％），女285名（39．1％），平均年龄为（26．6±11．4）岁。患者总体HLA—DQBl％0602阳性率为94．7％（1158／1223），其中猝倒组为97．0％（1098／1132），非猝倒组为65．9％（60／91）（r=155．4，P=0．000），三者均高于对照组的19．5％（142／728）。早发型患者阳性率为95．5％（990／1037），晚发型患者为90．1％（163／181）（X2=9．25，P=0．010）。hcrt缺失组阳性率为98．3％（113／115），hcrt正常组为25．6％（11／43）（X2=94．6，P=0．001）。结论HLA—DQB1＊0602在发作性睡病患者中阳性率高，伴有典型猝倒、早发以及hcrt缺失者阳性率更高。

Objective To explore the association of narcolepsy with human leukocyte histocompatibility antigen （HLA）-DQB1 ＊ 0602 allele in Chinese narcoleptic patients and examine its relationship with different phenotypes. Methods A total of 1 223 narcoleptic patients （ NC, narcolepsy with typical cataplexy, n = 1 132; NWC, narcolepsy without cataplexy, n = 91 ） diagnosed at Sleep Center of Peking University People＇s Hospital from August 1998 to July 2011 were recruited into this retrospective study. According to the onset age, they were divided into early-onset group （onset age ≤ 15y, n = 1 037） and late-onset group （onset age 〉 15y, n = 181 ）. All of them underwent a polymerase chain reaction with specific sequence primer （PCR-SSP） HLA-DQB1 ＊ 0602 typing. And the cerebrospinal fluid levels of hypocretin-1 （hcrt-1） were measured in 156 narcoleptic patients and they were divided into hcrt deficiency group （hcrt-1 〈 138 ng/L, n = 115） and hcrt normal group （ hcrt-1 ≥ 138 ng/L, n = 41 ）. And 728 healthy volunteers were selected as control group. The expression positivity of HLA-DQB1 ＊ 0602 gene was analyzed for each group. Results There were 1 223 narcoleptic patients including 825 males （67.5%） and 398 females （32. 5% ） with an average age of （ 16.6 ± 12. 6） years on visiting. There were 728 normal controls including 443 males （60. 9% ） and 285 females （39. 1% ） with an average age of （26. 6 ± 11.4） years on blood sampling. The positive rate of HLA-DQB1 ＊ 0602 in narcoleptic, NC and NWC groups was 94. 7% （1 158/1 223）, 97. 0% （1 098/1 132） and 65.9% （60/91） respective｜y. NC group had a higher rate of HLA-DQB1 ＊ 0602 positivity （X2 = 155.4, P = 0. 000）. Both groups were higher than that in control group of 19. 5% （142/728）. The positive rate of HLA-DQB1 ＊ 0602 in early-onset group was 95.5% （990/1 037） versus 90.1% （163/181） in late-onset group （）（2 = 9.25, P = 0.010）.Among those with hcrt-1 measurement, 98. 3% （113/115） were HLA-DQB1 ＊ 0602 positive in herr deficiency narcolepsy group versus 25.6% （11/43） in herr non-deficiency group （X2 = 94. 6, P = O. 001 ）. Conclusions HLA-DQB1 ＊ 0602 is an important marker in this large sample of Chinese patients with narcolepsy. Its frequency is much higher in patients with eataplexy, early-onset age and hcrt-1 deficiency.