中华风湿病学杂志
中華風濕病學雜誌
중화풍습병학잡지
CHINESE JOURNAL OF RHEUMATOLOGY
2014年
9期
583-588,651
,共7页
关节炎,幼年型类风湿%巨噬细胞活化综合征%基因
關節炎,幼年型類風濕%巨噬細胞活化綜閤徵%基因
관절염,유년형류풍습%거서세포활화종합정%기인
Arthritis,juvenile rheumatoid%Macrophage activation syndrome%Genes
目的 通过分析全身型幼年特发性关节炎(SoJIA)合并巨噬细胞活化综合征(MAS)患儿的临床资料及部分病例PRF1、UNC13D、STX11、STXBP2基因,揭示参与SoJIA并发MAS可能的遗传因素及SoJIA合并MAS相关临床特征.方法 收集整理2011年2月至2014年2月广州市妇女儿童医疗中心34例SoJIA合并MAS患儿的临床资料,扩增其中29例患儿PRF1、UNC13D、STX11、STXBP2基因所有参与编码的外显子序列后测序行序列分析.选择30名无血缘关系的健康儿童作为健康对照组.等位基因及基因型频率分布比较采用Pearson x2检验分析,以P＜0.05为差异有统计学意义.结果 34例SoJIA合并MAS患儿,其中男孩23例,中位年龄6岁.29例患儿行基因检测发现4个SNP位点.其中PRF1发现1个SNP位点c.1061C＞T(rs885822);UNC 13D基因发现1个SNP位点c.659 C＞T (rs3744007);STXBP2基因检测出2个SNP位点c.1483T＞C(rs10001)、c.1616 A＞G (rs6791).与健康对照组相比,病例组SNP位点PRF1基因rs885822基因型频率及等位基因频率差异有统计学意义(等位基因:x2=4.52,P=0.03;基因型:x2=5.52,P=0.02),STXBP2基因rs10001基因型频率及等位基因频率分布与对照组相比差异有统计学意义(等位基因:x2=21.33,P=0.00;基因型:x2=19.58,P=0.00).多态性位点UNC13D基因rs3744007及STXBP2基因rs6791基因型频率及等位基因频率与对照组对比差异无统计学意义(rs3744007等位基因:x2=1.89,P=0.17;基因型:x2=1.59,P=0.45;rs6791等位基因:x2=1.69,P=0.19;基因型:x2=2.09,P=0.35).研究中所有患儿皆有持续高热,进行性肝脾肿大,血细胞急剧减少,多发浆膜腔积液,血清肝酶显著升高,血脂代谢紊乱等特点.7例(21％)患儿出现黏膜出血、5例(15％)患儿出现神经系统功能异常等.28例(82％)患儿前期有上呼吸道感染病史,部分患儿检出特异病原体.经治疗,31例(90％)患儿病情缓解,3例患儿并发多器官功能衰竭死亡.结论 PRF1基因rs885822及STXBP2基因rs10001多态性位点可能与SoJIA并发MAS发病过程有关,该基因多态性是否和相应蛋白功能异常有关从而导致MAS发生,还需要进一步研究证实.
目的 通過分析全身型幼年特髮性關節炎(SoJIA)閤併巨噬細胞活化綜閤徵(MAS)患兒的臨床資料及部分病例PRF1、UNC13D、STX11、STXBP2基因,揭示參與SoJIA併髮MAS可能的遺傳因素及SoJIA閤併MAS相關臨床特徵.方法 收集整理2011年2月至2014年2月廣州市婦女兒童醫療中心34例SoJIA閤併MAS患兒的臨床資料,擴增其中29例患兒PRF1、UNC13D、STX11、STXBP2基因所有參與編碼的外顯子序列後測序行序列分析.選擇30名無血緣關繫的健康兒童作為健康對照組.等位基因及基因型頻率分佈比較採用Pearson x2檢驗分析,以P＜0.05為差異有統計學意義.結果 34例SoJIA閤併MAS患兒,其中男孩23例,中位年齡6歲.29例患兒行基因檢測髮現4箇SNP位點.其中PRF1髮現1箇SNP位點c.1061C＞T(rs885822);UNC 13D基因髮現1箇SNP位點c.659 C＞T (rs3744007);STXBP2基因檢測齣2箇SNP位點c.1483T＞C(rs10001)、c.1616 A＞G (rs6791).與健康對照組相比,病例組SNP位點PRF1基因rs885822基因型頻率及等位基因頻率差異有統計學意義(等位基因:x2=4.52,P=0.03;基因型:x2=5.52,P=0.02),STXBP2基因rs10001基因型頻率及等位基因頻率分佈與對照組相比差異有統計學意義(等位基因:x2=21.33,P=0.00;基因型:x2=19.58,P=0.00).多態性位點UNC13D基因rs3744007及STXBP2基因rs6791基因型頻率及等位基因頻率與對照組對比差異無統計學意義(rs3744007等位基因:x2=1.89,P=0.17;基因型:x2=1.59,P=0.45;rs6791等位基因:x2=1.69,P=0.19;基因型:x2=2.09,P=0.35).研究中所有患兒皆有持續高熱,進行性肝脾腫大,血細胞急劇減少,多髮漿膜腔積液,血清肝酶顯著升高,血脂代謝紊亂等特點.7例(21％)患兒齣現黏膜齣血、5例(15％)患兒齣現神經繫統功能異常等.28例(82％)患兒前期有上呼吸道感染病史,部分患兒檢齣特異病原體.經治療,31例(90％)患兒病情緩解,3例患兒併髮多器官功能衰竭死亡.結論 PRF1基因rs885822及STXBP2基因rs10001多態性位點可能與SoJIA併髮MAS髮病過程有關,該基因多態性是否和相應蛋白功能異常有關從而導緻MAS髮生,還需要進一步研究證實.
목적 통과분석전신형유년특발성관절염(SoJIA)합병거서세포활화종합정(MAS)환인적림상자료급부분병례PRF1、UNC13D、STX11、STXBP2기인,게시삼여SoJIA병발MAS가능적유전인소급SoJIA합병MAS상관림상특정.방법 수집정리2011년2월지2014년2월엄주시부녀인동의료중심34례SoJIA합병MAS환인적림상자료,확증기중29례환인PRF1、UNC13D、STX11、STXBP2기인소유삼여편마적외현자서렬후측서행서렬분석.선택30명무혈연관계적건강인동작위건강대조조.등위기인급기인형빈솔분포비교채용Pearson x2검험분석,이P＜0.05위차이유통계학의의.결과 34례SoJIA합병MAS환인,기중남해23례,중위년령6세.29례환인행기인검측발현4개SNP위점.기중PRF1발현1개SNP위점c.1061C＞T(rs885822);UNC 13D기인발현1개SNP위점c.659 C＞T (rs3744007);STXBP2기인검측출2개SNP위점c.1483T＞C(rs10001)、c.1616 A＞G (rs6791).여건강대조조상비,병례조SNP위점PRF1기인rs885822기인형빈솔급등위기인빈솔차이유통계학의의(등위기인:x2=4.52,P=0.03;기인형:x2=5.52,P=0.02),STXBP2기인rs10001기인형빈솔급등위기인빈솔분포여대조조상비차이유통계학의의(등위기인:x2=21.33,P=0.00;기인형:x2=19.58,P=0.00).다태성위점UNC13D기인rs3744007급STXBP2기인rs6791기인형빈솔급등위기인빈솔여대조조대비차이무통계학의의(rs3744007등위기인:x2=1.89,P=0.17;기인형:x2=1.59,P=0.45;rs6791등위기인:x2=1.69,P=0.19;기인형:x2=2.09,P=0.35).연구중소유환인개유지속고열,진행성간비종대,혈세포급극감소,다발장막강적액,혈청간매현저승고,혈지대사문란등특점.7례(21％)환인출현점막출혈、5례(15％)환인출현신경계통공능이상등.28례(82％)환인전기유상호흡도감염병사,부분환인검출특이병원체.경치료,31례(90％)환인병정완해,3례환인병발다기관공능쇠갈사망.결론 PRF1기인rs885822급STXBP2기인rs10001다태성위점가능여SoJIA병발MAS발병과정유관,해기인다태성시부화상응단백공능이상유관종이도치MAS발생,환수요진일보연구증실.
Objective To investigate the clinical characteristics of 34 systemic onset juvenile idiopathic arthritis (SoJIA) complicated with macrophage activation syndrome (MAS) and analyzed the gene PRF1,UNC13D,STX11,STXBP2 to figure out the genetic pathogenesis mechanism.Methods The clinical characteristics of 34 SoJIA complicated with MAS were analyzed retrospectively and coding sequences of PRF1,UNC13D,STX11 were amplified and tested.The Chi-square test was applied to compare the distribution of alleles and genotypes frequencies between SLE patients and healthy controls.Statistical significance was defined as P value ＜0.05.Results A total number of 34 SoJIA complicated with MAS were included.Boys accounted for 69％(23/34),and the median age was 6 years.85％(29/34) cases had genetic tests and four SNPS loci were detected:PRF1 c.1061 C＞T (rs885822); UNC13D c.659 C＞T (rs3744007); STXBP2 c.1483 T＞cC (rs10001) and STXBP2 c.1616 A＞G (rs6791).Compared with the control group,genotype and allele frequency of PRF1 rs885822 and STXBP2 rs10001 in MAS cases were statistical significantly different (rs885822:allele frequency x2=4.52,P=0.03 ; genotype frequency:x2=5.52,P=0.02.rs10001:allele frequencyx2=21.33,P=0.00; genotype frequency:x2=19.58,P=0.00).There was no statistical significant difference in genotype frequency and allele frequency of UNC13D rs3744007 and STXBP2 rs6791 between the MAS and control group (rs3744007:allele frequencyx2=1.89,P=0.17; genotype frequency:x2=1.59,P=0.45.rs6791:allele frequency x2=l.69,P=0.19; genotype frequency:x2=2.09,P=0.35).Persistent fever,progressive hepatos-plenomegaly,a sharp decline in blood cells counts,pleural effusion,markedly increased serum liver enzymes,hyperlipidemia were the main characteristics.Some children had mucosal bleeding,neurological dysfunction.More than 82％ children had upper respiratory tract infection before the occurrence of MAS.90％ of children were in remission,while three children had multiple organ failure and died.Conclusion MAS is a fatal complication caused by immune disturbance.Early detection and tre-atment is the key to improve the prognosis.The SNP PRF1 rs885822 and STXBP2 rs1001 may be concurrent with the pathogenesis of SoJIA-MAS.The SNP UNC13D rs3744007 and STXBP2 rs6791 may not participate in the pathogenesis of SoJIA-MAS.
