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.