CAJ | 학술논문

目的探讨人类白细胞抗原(HLA)DQB1启动子和编码子在Vogt-Koyanagi-Harada(VKH)综合征发病中的作用.方法 88例汉族VKH综合征患者和88名正常对照者纳入本研究.VKH综合征患者中,男性41例,女性47例,发病年龄15～67岁,平均年龄(36±11)岁.正常对照者中,男性42例,女性46例,年龄24～68岁,平均年龄(41±19)岁.采用聚合酶链式反应-序列特异性引物(PCR-SSP)方法进行HLA-DQB1等位基因分型,聚合酶链式反应-单链构象多态性(PCR-SSCP)-克隆-测序法检测HLA-DQB1基因启动子区(HLA-QBP)等位基因.应用x2检验或Fisher精确概率法进行统计分析.结果 VKH综合征患者中HLA-DQB1*0401(0.318比0.045,x2=44.00,P=0.000,OR=9.8)和DQB1*0303(0.068比0.006,x2=9.67,P=0.002,OR=12.81)频率明显高于正常对照者,差异有统计学意义.而HLA-DQB1*0601(0.017比0.096,x2=10.39,P=0.001,OR=0.16)和HLA-DQB1*0302(0.063比0.193,x2=13.48,P=0.000,OR=0.28)在VKH综合征患者中出现的频率显著低于正常对照者,差异有统计学意义.VKH综合征患者HLA-DQB1基因启动子区-189C/A的C等位基因频率显著高于正常对照者(0.324比0.074,x2=45.92,P=0.000),而-227G/A等位基因频率低于正常对照者(0.011比0.108,x2=15.63,P=0.000).VKH综合征患者中易感等位基因的组合(-189C和HLA-DQB1*0401)频率明显高于正常对照者,正常对照者中抗性等位基因的组合(-227G和HLA-DQB1*0601)频率显著高于VKH综合征患者.结论 VKH综合征发病可能与HLA-DQB1启动子和编码区相互作用有关.
목적 탐토인류백세포항원(HLA)DQB1계동자화편마자재Vogt-Koyanagi-Harada(VKH)종합정발병중적작용.방법 88례한족VKH종합정환자화88명정상대조자납입본연구.VKH종합정환자중,남성41례,녀성47례,발병년령15～67세,평균년령(36±11)세.정상대조자중,남성42례,녀성46례,년령24～68세,평균년령(41±19)세.채용취합매련식반응-서렬특이성인물(PCR-SSP)방법진행HLA-DQB1등위기인분형,취합매련식반응-단련구상다태성(PCR-SSCP)-극륭-측서법검측HLA-DQB1기인계동자구(HLA-QBP)등위기인.응용x2검험혹Fisher정학개솔법진행통계분석.결과 VKH종합정환자중HLA-DQB1*0401(0.318비0.045,x2=44.00,P=0.000,OR=9.8)화DQB1*0303(0.068비0.006,x2=9.67,P=0.002,OR=12.81)빈솔명현고우정상대조자,차이유통계학의의.이HLA-DQB1*0601(0.017비0.096,x2=10.39,P=0.001,OR=0.16)화HLA-DQB1*0302(0.063비0.193,x2=13.48,P=0.000,OR=0.28)재VKH종합정환자중출현적빈솔현저저우정상대조자,차이유통계학의의.VKH종합정환자HLA-DQB1기인계동자구-189C/A적C등위기인빈솔현저고우정상대조자(0.324비0.074,x2=45.92,P=0.000),이-227G/A등위기인빈솔저우정상대조자(0.011비0.108,x2=15.63,P=0.000).VKH종합정환자중역감등위기인적조합(-189C화HLA-DQB1*0401)빈솔명현고우정상대조자,정상대조자중항성등위기인적조합(-227G화HLA-DQB1*0601)빈솔현저고우VKH종합정환자.결론 VKH종합정발병가능여HLA-DQB1계동자화편마구상호작용유관.
Objective To investigate the genetic interaction of HLA-DQB1 promoter and coding alleles in the pathogenesis of Vogt-Koyanagi-Harada syndrome (VKH). Methods Eighty-eight Chinese Han patients with VKH and eighty-eight non-VKH normal controls were enrolled in this study. DNA was extracted from white blood cells of the subjects by phenol-chloroform method. Thirteen alleles were genotyped by polymerase chain reaction-sequence-specific primers (PCR-SSP), polymerase chain reactionsingle strand conformation polymorphism (PCR-SSCP) and clone-sequencing was applied to determine the polymorphisms of the promoter and coding regions of HLA-DQB1 gene. Chromas and Bioedit software were used to analyze the sequences of the promoter of HLA-DQB1. Chi-square test and Fisherexact test were the statistical methods. Relationships among single nucleotide polymorphism (SNP) in the promoter and coding region were analyzed. Results Twelve of thirteen already known HLA-DQB1 alleles were genotyped by PCR-SSP in VKH patients. The most frequent allele in VKH patients was HLA-DQB1 * 0401 (0.318,44.00, P=0.000, OR=9.8). So was for HLA-DQB1*0303 (0.068 vs. 0.006, x2=9.67, P=0.002,OR=12.81). In contrast, the frequency of HLA-DQB1*0601 (0.017 vs. 0.096, x2=10.39, P=0.001,OR=0.16) and HLA-DQB1 * 0302 (0.062 vs. 0.193, x2=13.48, P=0.000, OR=0.28) in VKH patients were significantly lower than normal controls. Twelve SNP were found in all subjects. The frequency of C allele at position - 189C/A in VKH patients was significantly higher than that in controls (0.324 vs. 0.074, x2=45.92, P=0.000). However, the frequency of G allele at position -227G/A in VKH patients was significantly lower than that in the normal controls (0.011 vs. 0.108, x2=15.63, P=0.000). The frequency of combination of susceptible alleles in promoter and coding area (-189C and HLA-DQB1 * 0401) in VKH patients was statistically higher than that in controls, the frequency of combination of resistant alleles in control (-227G and HLA-DQB1 * 0601) was higher than that in VKH patients.Conclusions The specific interactions of SNP in the promoter and coding alleles of HLA-DQB1 are associated with the pathogenesis of VKH.