Center of Maternal and Child Health Care, First Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, People's Republic of China.
J Bone Joint Surg Am. 2010 Jan;92(1):72-80. doi: 10.2106/JBJS.H.00502.
The etiology of Kashin-Beck disease, an endemic osteochondropathy, is unknown. Environmental factors, including selenium deficiency, have been proposed as potential risk factors, but the onset and frequency of this disease vary among groups with similar environmental exposures. Some cases of osteoarthritis that share similar pathological features with Kashin-Beck disease have been associated with specific chromosomal short tandem repeats. In order to better understand the pathogenesis of Kashin-Beck disease, we examined fifteen short tandem-repeat loci on chromosomes 2 and 11 in patients and control subjects, and assessed the interaction between genetic variants and selenium deficiency.
DNA samples from 129 patients with Kashin-Beck disease (the Kashin-Beck disease group), seventy-two healthy control subjects from areas where Kashin-Beck disease was endemic (control group 1), and forty-eight healthy control subjects from areas where Kashin-Beck disease was not endemic (control group 2) were collected, and fifteen short tandem repeats were genotyped. The allele frequencies of these short tandem-repeat loci were compared among the three groups. Differences in selenium concentrations among patients and controls were also examined, and the interaction between low selenium levels and the susceptibility loci was calculated.
The percentages of subjects with short tandem-repeat alleles D2S338 (290 bp) and D11S4094 (194 bp) in the Kashin-Beck disease group were significantly lower than those in the two control groups, while percentages of D2S305 (320 bp) and D11S4149 (221 bp) were higher than those in the control groups. The percentage of subjects with D11S4149 (217 bp) in the Kashin-Beck disease group was only significantly lower than that in control group 1. The percentages of subjects with D11S912 (106 bp) in both the Kashin-Beck disease group and control group 1 were significantly lower than those in control group 2. Selenium concentrations in serum from subjects in the Kashin-Beck disease group and control group 1 were similar, but both were lower than that of control group 2. The odds ratios of low selenium in serum were between 1.2 and 1.6 (p > 0.05), and the odds ratios of interactions between low selenium and the susceptibility loci ranged between 0.8 and 1.4 (p > 0.05).
Our results suggest that variants of the chromosomal short tandem repeats D11S4094, D11S4149, D2S338, and D2S305 are associated with Kashin-Beck disease, and that the frequency of D11S912 polymorphisms varies in geographic areas with high and low prevalences of Kashin-Beck disease. Our data did not show a significant interaction between low selenium and the susceptibility loci in the occurrence of Kashin-Beck disease. The interaction between genetic variabilities and environmental factors can be complex, but our results suggest that genetic factors may be more important than selenium deficiency in the pathogenesis of Kashin-Beck disease.
地方性骨软骨病卡森-贝克病的病因不明。环境因素，包括硒缺乏，已被提出作为潜在的危险因素，但这种疾病的发病和频率在具有相似环境暴露的人群中有所不同。一些与卡森-贝克病具有相似病理特征的骨关节炎病例与特定的染色体短串联重复序列有关。为了更好地了解卡森-贝克病的发病机制，我们在患者和对照组中检查了 2 号和 11 号染色体上的 15 个短串联重复序列，并评估了遗传变异与硒缺乏之间的相互作用。
收集了 129 名卡森-贝克病患者（卡森-贝克病组）、72 名来自卡森-贝克病流行地区的健康对照组（对照组 1）和 48 名来自卡森-贝克病非流行地区的健康对照组（对照组 2）的 DNA 样本，并对 15 个短串联重复序列进行了基因分型。比较了三组短串联重复序列的等位基因频率。还检查了患者和对照组之间的硒浓度差异，并计算了低硒水平与易感基因座之间的相互作用。
卡森-贝克病组的短串联重复序列等位基因 D2S338（290bp）和 D11S4094（194bp）的个体比例明显低于两个对照组，而 D2S305（320bp）和 D11S4149（221bp）的个体比例高于对照组。卡森-贝克病组中 D11S4149（217bp）的个体比例仅明显低于对照组 1。卡森-贝克病组和对照组 1 中 D11S912（106bp）的个体比例明显低于对照组 2。卡森-贝克病组和对照组 1 血清中的硒浓度相似，但均低于对照组 2。血清中低硒的比值比在 1.2 到 1.6 之间（p>0.05），低硒与易感基因座之间的相互作用比值在 0.8 到 1.4 之间（p>0.05）。
我们的结果表明，染色体短串联重复序列 D11S4094、D11S4149、D2S338 和 D2S305 的变异与卡森-贝克病有关，D11S912 多态性的频率在卡森-贝克病高发和低发地区有所不同。我们的数据没有显示低硒与易感基因座在卡森-贝克病发生中的显著相互作用。遗传变异性和环境因素之间的相互作用可能很复杂，但我们的结果表明，遗传因素可能比硒缺乏在卡森-贝克病的发病机制中更为重要。
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