Barron K S, Reveille J D, Carrington M, Mann D L, Robinson M A
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Arthritis Rheum. 1995 May;38(5):684-9. doi: 10.1002/art.1780380517.
Although HLA-B27 is strongly associated with susceptibility to Reiter's syndrome (RS), recent data suggest that an additional modifying or susceptibility gene(s) acts in concert with HLA-B27 to contribute to disease pathogenesis. The recently described TAP genes (transporters associated with antigen processing) are potential candidates because they are polymorphic and their function is to transport antigenic peptides to be loaded in HLA class I molecules.
TAP1 and TAP2 alleles were determined for 34 patients with RS (28 HLA-B27 positive, 6 HLA-B27 negative), and their frequencies were compared with those observed for 52 HLA-B27 positive and 80 random disease-free control subjects.
The allele frequency of TAP1C was greater in patients with RS (8 of 62, 13%) than in random controls (5 of 160, 3%) (P = 0.009). The frequency of TAP2A was greater in RS patients (51 of 66, 77%) than in random controls (88 of 160, 55%) (P = 0.002); likewise, the frequency was greater in HLA-B27 positive RS patients (41 of 54, 76%) than in HLA-B27 positive disease-free controls (49 of 94, 52%) (P = 0.004). Furthermore, the TAP2A allele was present in all RS patients (100%), whereas TAP2A was present in 79% (63 of 80) of the random controls (P = 0.003).
The association observed between TAP alleles and RS is independent of the presence of HLA-B27, and despite the physical proximity of TAP and HLA class II genes, linkage disequilibrium does not account for the observed associations between TAP and RS. Thus, TAP genes are genetically separated but functionally linked to class I genes, and both contribute to susceptibility to RS.
尽管HLA - B27与赖特综合征（RS）易感性密切相关，但近期数据表明，另一个修饰基因或易感基因与HLA - B27协同作用，参与疾病发病机制。最近描述的TAP基因（与抗原加工相关的转运体）是潜在候选基因，因为它们具有多态性，其功能是转运抗原肽以加载到HLA I类分子中。
测定了34例RS患者（28例HLA - B27阳性，6例HLA - B27阴性）的TAP1和TAP2等位基因，并将其频率与52例HLA - B27阳性和80例随机无病对照者的观察频率进行比较。
RS患者中TAP1C的等位基因频率（62例中的8例，13%）高于随机对照者（160例中的5例，3%）（P = 0.009）。RS患者中TAP2A的频率（66例中的51例，77%）高于随机对照者（160例中的88例，55%）（P = 0.002）；同样，HLA - B27阳性RS患者中TAP2A的频率（54例中的41例，76%）高于HLA - B27阳性无病对照者（94例中的49例，52%）（P = 0.004）。此外，所有RS患者中均存在TAP2A等位基因（100%），而随机对照者中有79%（80例中的63例）存在TAP2A（P = 0.003）。
观察到的TAP等位基因与RS之间的关联独立于HLA - B27的存在，尽管TAP与HLA II类基因在物理位置上接近，但连锁不平衡并不能解释观察到的TAP与RS之间的关联。因此，TAP基因在遗传上是分离的，但在功能上与I类基因相关联，并都参与了RS的易感性。
