González S, Torre-Alonso J C, Martínez-Borra J, Fernández Sánchez J A, López-Vazquez A, Rodríguez Pérez A, López-Larrea C
Department of Immunology, Hospital Central de Asturias, E-33006 Oviedo, Spain.
J Rheumatol. 2001 Jun;28(6):1288-93.
To investigate the relative contribution of MHC loci in their susceptibility to primary ankylosing spondylitis (AS) in HLA-B27 negative patients and to compare the clinical features and genetic factors with those of HLA-B27 positive AS.
DNA from patients with B27 negative primary AS (n = 28), B27 positive primary AS (n = 77), and matched healthy controls (B27-, n = 100; B27+, n = 70) were analyzed to investigate whether HLA genes determine the disease susceptibility, or whether other closely linked loci might play a role in disease development. HLA typing was carried out by serology and PCR/SSP (HLA-B, -DR), MICA-TM polymorphism in the transmembrane region by radioactive PCR, and tumor necrosis factor-alpha (TNF-alpha) promoter polymorphism at positions -238 and -308 by PCR-RFLP.
Subtle clinical differences were found for primary AS, the B27 negative patients being less frequently complicated by acute anterior uveitis and more associated with peripheral arthritis than B27 positive. Differences were found in the distribution of TNF-alpha -238 genotypes among patients with primary AS (B27- vs B27+). The TNF-alpha -238(A) polymorphism was present in 50% of the B27 negative patients carrying the -238 G/A and A/A genotypes and was significantly increased compared with B27 positive AS (odds ratio 4.3) and with the B27 negative control group (OR 5.9). The TNF-alpha genotypes were equally prevalent in B27 positive AS and healthy matched B27 positive controls. No significant HLA and MICA typing differences were found between the populations under study.
Our results indicate that the polymorphism variation in the TNF-alpha promoter -238.2(A) influences disease susceptibility in B27 negative primary AS but had no effect in our B27 positive AS population.
研究MHC基因座在HLA - B27阴性原发性强直性脊柱炎（AS）患者易感性中的相对作用，并比较其与HLA - B27阳性AS患者的临床特征和遗传因素。
分析B27阴性原发性AS患者（n = 28）、B27阳性原发性AS患者（n = 77）及匹配的健康对照者（B27阴性，n = 100；B27阳性，n = 70）的DNA，以研究HLA基因是否决定疾病易感性，或其他紧密连锁的基因座是否在疾病发展中起作用。通过血清学和PCR/SSP（HLA - B、- DR）进行HLA分型，通过放射性PCR检测跨膜区的MICA - TM多态性，通过PCR - RFLP检测肿瘤坏死因子 - α（TNF - α）启动子在 - 238和 - 308位点的多态性。
原发性AS存在细微的临床差异，B27阴性患者急性前葡萄膜炎并发症较少，与外周关节炎的相关性比B27阳性患者更强。原发性AS患者（B27阴性与B27阳性）之间TNF - α - 238基因型分布存在差异。携带 - 238 G/A和A/A基因型的B27阴性患者中，50%存在TNF - α - 238(A)多态性，与B27阳性AS患者（优势比4.3）和B27阴性对照组（OR 5.9）相比显著增加。TNF - α基因型在B27阳性AS患者和匹配的B27阳性健康对照者中同样普遍。在所研究的人群之间未发现显著的HLA和MICA分型差异。
我们的结果表明，TNF - α启动子 - 238.2(A)的多态性变异影响B27阴性原发性AS患者的疾病易感性，但对我们研究的B27阳性AS人群无影响。
