Kim Tae-Hwan, Kim Tae-Jong, Lee Hye-Soon, Uhm Wan-Sik, Shin Eun-Soon, Na Young-In, Jun Jae-Bum
Hospital for Rheumatic Diseases, Hanyang University, Seoul, Republic of Korea.
J Rheumatol. 2008 Sep;35(9):1849-52. Epub 2008 Jul 15.
To investigate the genetic association between ankylosing spondylitis (AS) and single nucleotide polymorphisms (SNP) of collagen 6A1 gene (COL6A1), the candidate gene for ossification of the posterior longitudinal ligament.
One-hundred thirty Korean patients with AS (M: 116, F: 14, age: 29.0 +/- 4.6) and 130 age- and sex-matched healthy subjects were recruited. The SNP of G365G, IVS15+39 C/T, IVS21+18 A/C by Snap shot assay and the SNP of IVS32-29T/C, IVS33+15G/A, IVS33+20A/G, and IVS33+55A/G by direct sequencing were genotyped and analyzed. Bonferroni correction was applied to multiple comparisons.
The observed allelic frequencies for these SNP met Hardy-Weinberg equilibrium in all AS and controls. We also found an additional 2 SNP (R783Q and IVS33+88C/T) during direct sequencing. Therefore, a total of 9 SNP were analyzed in this study. There were no significant associations of allelic and genotype variations between AS and controls. The presence of uveitis was marginally associated with a haplotype (CC in G365G + IVS15+39 C/T). The variation of allele or haplotype of COL6A1 is not significantly associated with "more ossified disease."
Because the genetic variations of COL6A1 could not be correlated with the occurrence of AS in Koreans, we conclude that despite common clinical features, AS and ossification of posterior longitudinal ligament are not genetically related, and the hyperostotic condition seen in the 2 diseases might be regulated differently. Further SNP of COL6A1 were not related to radiographic progression of AS. However, we found that the occurrence of uveitis might be related to the genetic variations of COL6A1 in patients with AS.
研究强直性脊柱炎（AS）与后纵韧带骨化候选基因胶原蛋白6A1基因（COL6A1）单核苷酸多态性（SNP）之间的遗传关联。
招募130例韩国AS患者（男：116例，女：14例，年龄：29.0±4.6岁）和130例年龄及性别匹配的健康对照。通过Snap shot分析法对G365G、IVS15+39 C/T、IVS21+18 A/C的SNP以及通过直接测序对IVS32-29T/C、IVS33+15G/A、IVS33+20A/G和IVS33+55A/G的SNP进行基因分型和分析。对多重比较采用Bonferroni校正。
在所有AS患者和对照中，这些SNP的观察等位基因频率符合Hardy-Weinberg平衡。在直接测序过程中我们还发现了另外2个SNP（R783Q和IVS33+88C/T）。因此，本研究共分析了9个SNP。AS患者与对照之间的等位基因和基因型变异无显著关联。葡萄膜炎的存在与一种单倍型（G365G + IVS15+39 C/T中的CC）存在边缘关联。COL6A1等位基因或单倍型的变异与“骨化更严重的疾病”无显著关联。
由于COL6A1的基因变异与韩国人AS的发生无关，我们得出结论，尽管AS和后纵韧带骨化有共同的临床特征，但它们在遗传上并无关联，这两种疾病中出现的骨质增生情况可能受到不同的调节。COL6A1的进一步SNP与AS的影像学进展无关。然而，我们发现葡萄膜炎的发生可能与AS患者COL6A1的基因变异有关。
