Zhang Yanli, Liao Zetao, Wei Qiujing, Pan Yunfeng, Wang Xinwei, Cao Shuangyan, Guo Zishi, Wu Yuqiong, Rong Ju, Jin Ou, Xu Manlong, Lin Zhiming, Gu Jieruo
Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China.
PLoS One. 2016 Dec 14;11(12):e0166888. doi: 10.1371/journal.pone.0166888. eCollection 2016.
To screen susceptibility loci for ankylosing spondylitis (AS) using an affected-only linkage analysis based on high-density single nucleotide polymorphisms (SNPs) in a genome-wide manner.
AS patients from ten families with Cantonese origin of China were enrolled in the study. Blood samples were genotyped using genomic DNA derived from peripheral blood leukocytes by Illumina HumanHap 610-Quad SNP Chip. Genotype data were generated using the Illumina BeadStudio 3.2 software. PLINK package was used to remove non-autosomal SNPs and to further eliminate markers of typing errors. An affected-only linkage analysis was carried out using both non-parametric and parametric linkage analyses, as implemented in MERLIN.
Seventy-eight AS patients (48 males and 30 females, mean age: 39±16 years) were enrolled in the study. The mean age of onset was 23±10 years and mean duration of disease was 16.7±12.2 years. Iritis (2/76, 2.86%), dactylitis (5/78, 6.41%), hip joint involvement (9/78, 11.54%), peripheral arthritis (22/78, 28.21%), inflammatory back pain (IBP) (69/78, 88.46%) and HLA-B27 positivity (70/78, 89.74%) were observed in these patients. Using non-parameter linkage analysis, we found one susceptibility locus for AS, IBP and HLA-B27 in 6p21 respectively, spanning about 13.5Mb, 20.9Mb and 21.2Mb, respectively No significant results were found in the other clinical trait groups including dactylitis, hip involved and arthritis. The identical susceptibility locus region spanning above 9.44Mb was detected in AS IBP and HLA-B27 by the parametric linkage analysis.
Our genome-wide SNP linkage analysis in ten families with ankylosing spondylitis suggests a susceptibility locus on 6p21 in AS, which is a risk locus for IBP in AS patients.
采用仅基于受累个体的连锁分析方法，利用全基因组范围内的高密度单核苷酸多态性（SNP）筛查强直性脊柱炎（AS）的易感基因座。
招募了来自中国广东的十个家庭的AS患者参与本研究。使用Illumina HumanHap 610-Quad SNP芯片对来源于外周血白细胞的基因组DNA进行基因分型。使用Illumina BeadStudio 3.2软件生成基因型数据。使用PLINK软件包去除非常染色体SNP，并进一步消除分型错误的标记。使用MERLIN软件中实现的非参数和参数连锁分析方法进行仅基于受累个体的连锁分析。
本研究共纳入78例AS患者（48例男性，30例女性，平均年龄：39±16岁）。平均发病年龄为23±10岁，平均病程为16.7±12.2年。这些患者中观察到虹膜炎（2/76，2.86%）、指（趾）炎（5/78，6.41%）、髋关节受累（9/78，11.54%）、外周关节炎（22/78，28.21%）、炎性腰背痛（IBP）（69/78，88.46%）和HLA-B27阳性（70/78，89.74%）。使用非参数连锁分析，我们分别在6p21区域发现了一个AS、IBP和HLA-B27的易感基因座，分别跨越约13.5Mb、20.9Mb和21.2Mb。在包括指（趾）炎、髋关节受累和关节炎在内的其他临床特征组中未发现显著结果。通过参数连锁分析在AS、IBP和HLA-B27中检测到跨越9.44Mb以上的相同易感基因座区域。
我们对十个强直性脊柱炎家庭进行的全基因组SNP连锁分析表明，AS患者6p21上存在一个易感基因座，该基因座是AS患者IBP的风险基因座。
