Lu Ming-Chi, Yang Kuo-Liang, Huang Kuang-Yung, Tung Chien-Hsueh, Liu Su-Qin, Lai Ning-Sheng
Department of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Buddhist Hospital, City of Chia Yi, Taiwan.
Dis Markers. 2009;26(2):93-6. doi: 10.3233/DMA-2009-0619.
To evaluate the possible relationship between HLA alleles and bony ankylosis of the spine (bamboo spine) in Taiwanese patients with ankylosing spondylitis (AS).
A small cohort of HLA-B27 positive AS patients was conducted to analyze the effects of alleles {and haplotypes} on the development of bamboo spine. DNA typing of HLA class I and class II genes were performed by SSP method on primary ankylosing spondylitis patients with bamboo spine (n = 84) and spinal enthesopathy controls (n = 228). Odds ratios with 95% confidence intervals and P value were estimated. Determination of the most probable HLA haplotypes on all patients were constructed by comparison of the alleles carried by each patient with the HLA haplotype database established in Taiwanese population studies using homozygosity approach [1] and by expectation-maximum algorithm [2].
Allele frequencies of HLA A33, B58, Cw10, DR4, DR17 and DQ2 were significantly lower in bamboo patients as compared to non-bamboo controls. In contrast, allele frequencies of A24, B54, Cw15, DR11 and DR14 were significantly higher in bamboo patients. Less remarkably, high frequencies of B39, B51, Cw1 and Cw2 alleles were also noted in bamboo patients. Considering linkage disequilibria of alleles in haplotypes, HLA-A11-B27-Cw12 was the most common haplotype in both bamboo and non-bamboo groups (95.23% vs. 91.22%, respectively, P = 0.238). {Haplotypes A33-B58-Cw10, A33-B58-Cw10-DR13 and A33-B58-Cw10-DR17} were significantly lower in bamboo patients as compared to those in controls (P < 0.001, P = 0.001, P = 0.002, respectively).
Haplotypes A33-B58-Cw10, A33-B58-Cw10-DR13 and A33-B58-Cw10-DR17 showed a strong association with bamboo spine in Taiwanese AS patients. Detection of such haplotypes might be a great aid in the management of patients with the disease.
评估台湾强直性脊柱炎(AS)患者中HLA等位基因与脊柱骨性强直(竹节样脊柱)之间的可能关系。
对一小群HLA - B27阳性的AS患者进行研究,分析等位基因{和单倍型}对竹节样脊柱形成的影响。采用序列特异性引物(SSP)方法,对84例患有竹节样脊柱的原发性强直性脊柱炎患者和228例脊柱附着点病对照者进行HLA I类和II类基因的DNA分型。计算比值比及95%置信区间和P值。通过将每位患者携带的等位基因与台湾人群研究中建立的HLA单倍型数据库进行比较,采用纯合性方法[1]和期望最大化算法[2],确定所有患者最可能的HLA单倍型。
与非竹节样脊柱对照组相比,竹节样脊柱患者中HLA A33、B58、Cw10、DR4、DR17和DQ2的等位基因频率显著降低。相反,竹节样脊柱患者中A24、B54、Cw15、DR11和DR14的等位基因频率显著升高。不太明显的是,竹节样脊柱患者中B39、B51、Cw1和Cw2等位基因的频率也较高。考虑到单倍型中等位基因的连锁不平衡,HLA - A11 - B27 - Cw12是竹节样脊柱组和非竹节样脊柱组中最常见的单倍型(分别为95.23%和91.22%,P = 0.238)。{与对照组相比,竹节样脊柱患者中A33 - B58 - Cw10、A33 - B58 - Cw10 - DR13和A33 - B58 - Cw10 - DR17单倍型}显著降低(P分别< 0.001、P = 0.001、P = 0.002)。
A33 - B58 - Cw10、A33 - B58 - Cw10 - DR13和A33 - B58 - Cw10 - DR17单倍型与台湾AS患者的竹节样脊柱密切相关。检测这些单倍型可能对该病患者的管理有很大帮助。