抗原处理相关转运体等位基因与HLA-B27检测呈阳性的强直性脊柱炎的相关研究

摘要

Objective　To investigate the association between transporter associated with antigen processing(TAP) gene and ankylosing spondylitis(AS) as well as HLA-B27. Methods　 PCR-SSO was used to analyze the frequencies of TAP alleles and variant amino acids of TAP in 48 patients (B27+) with AS and 123 normal individuals (B27+ or B27-). Results　 The phenotypes of Ile/Ile, Asp/Asp were over-presented for TAP1 and Val/Val, Ala/Thr, Stop/Stop for TAP2 in Han nationality. For each TAP there were four alleles: TAP1*0101, TAP1*0201, TAP1*0301, TAP1*0401, and TAP2*0101, TAP2*0102, TAP2*0201, TAP2*0202. In the research subjects, hybridization blanks accounted for 9.9%(17/171) of TAP1 and 15.8%(27/171) of TAP2. No difference was found in the distribution of TAP alleles between the AS patients(B27+) and normal controls(B27+ or B27-). In the patients group the frequency of phenotype in codon of 333 (Val/Val) was significantly decreased as compared with that of the healthy controls(B27+)(P＜0.05). In addition, the frequency of phenotype Ala/Ala(665) was significantly decreased and that of Ala/Thr was significantly increased in normal controls(B27-), compared with those in normal controls(B27+)(P<0.05). Conclusion　 It is possible that there are new TAP alleles in Han nationality. No association was found between TAP alleles and AS. And the homozygosity for codon 333 which is Val/Val seems to offer resistance to AS among those HLA-B27+ individuals. In normal individuals, negative correlation was found between heterozygote Ala/Thr and B27, and possibly there was positive correlation between phenotype Ala/Ala and B27.%目的探讨汉族人群抗原处理相关转运体(transporter associated with antigen processing, TAP)等位基因与HLA-B27及强直性脊柱炎(ankylosing spondylitis, AS)的相关性。方法用聚合酶链反应-序列特异性寡核苷酸探针杂交技术，对48例AS患者(B27+)及123名正常对照人群(B27+27名、B27-96名)进行TAP1、TAP2等位基因分型及变异位点氨基酸表型频率分析。结果汉族人群TAP1表现型主要为Ile/Ile和Asp/Asp，而TAP2则以Val/Val、Ala/Thr和Stop/Stop占优势。TAP1和TAP2至少各有4种等位基因型，分别为TAP1*0101、TAP1*0201、TAP1*0301、TAP1*0401和TAP2*0101、TAP2*0102、TAP2*0201、TAP2*0202。研究对象中有9.9%(17/171)TAP1探针无法定型，15.8%(27/171)TAP2无法定型，呈杂交空白。病例组与对照组间TAP等位基因型分布无差异(P＞0.05)。AS(B27+)患者TAP1 333位纯合子Val/Val表型频率显著低于正常对照(B27+)(P＜0.05)。正常对照(B27+)TAP2 665位纯合子Ala/Ala表型频率显著高于正常对照(B27-)(P＜0.05)，而正常对照(B27+)TAP2 665位杂合子Ala/Thr表型频率则显著低于正常对照(B27-)(P＜0.05)。结论汉族人群中可能存在新的TAP等位基因。未证明TAP等位基因型与AS相关。HLA-B27+个体中，纯合子表型Val/Val呈AS抗性。在正常人群中纯合子表型Ala/Ala可能与B27正相关，杂合子表型Ala/Thr与B27负相关。