Humans ; Female ; Tibet ; Kashin-Beck Disease/epidemiology* ; China ; Metabolomics

Adolescent ; Amino Acids ; urine ; Child ; Female ; Humans ; Kashin-Beck Disease ; urine ; Male ; Metabolomics

BACKGROUNDKashin-Beck disease (KBD) is a chronic, degenerative osteoarthropathy that causes severe skeletal deformation. Although many researchers have proven that almost all KBD patients who showed an increaseing proximo-distal gradient had radiographic abnormalities of the ankle, few detailed description of radiographic changes in the ankles of patients with KBD has been reported, especially for variable measurements of ankle changes. The purpose of this study was to demonstrate the radiographic characteristics of the ankles of adult KBD patients.

METHODSOne hundred and eighteen adult KBD patients from september to October 2010 in Rongtang county in China were examined with lateral radiographs of the right ankle. The morphological abnormalities in the talus, calcaneus, navicular bone, distal tibia, and joint space were analyzed, and the calcaneus length, height, length-height ratio, tuber angle, front angle, plantar angle, and distal tibia anteroposterior (AP) length were measured using Riepert's method.

RESULTSEighty-one patients (68.6%) had abnormal ankle radiographs; 72 (88.9%) patients had talus changes, 69 (85.2%) patients had calcaneus changes, 28 (34.6%) patients had navicular bone changes, and 48 (59.2%) patients had distal tibia changes. For 118 KBD patients, the average calcaneus length was 7.4 cm, height was 4.3 cm, and the length-height ratio was 1.7. The calcaneus tuber angle was 28.2°, front angle was 38.0° and the plantar angle was 74.2°. The distal tibia anteroposterior length was 4.05 cm. Compared with 50 normal adults (control group), significant differences were found for the calcaneus length, the calcaneus length-height ratio, and the distal tibia AP length.

CONCLUSIONSPatients with KBD have characteristic abnormalities on ankle radiographs; talus depression and deformity, calcaneus shortening deformity, and distal tibia deformity with AP length widening were the most typical changes.

Adult ; Aged ; Ankle ; diagnostic imaging ; Female ; Humans ; Kashin-Beck Disease ; diagnostic imaging ; Male ; Middle Aged ; Radiography ; Young Adult

Objective: To explore potential serum biomarkers of children with Kashin-Beck Disease (KBD) and the metabolic pathways to which the biomarkers belong. Methods: A two-stage metabolomic study was employed. The discovery cohort included 56 patients, 51 internal controls, and 50 external controls. The metabolites were determined by HPLC-(Q-TOF)-MS and confirmed by Human Metabolome Databases (HMDB) and Metlin databases. MetaboAnalyst 3.0 and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used to analyze the metabolic pathways of the candidate metabolites. The use of HPLC-(Q-TRAP)-MS enabled quantitative detection of the target metabolites which were chosen using the discovery study and verified in another independent verification cohort of 31 patients, 41 internal controls, and 50 external controls. Results: Eight candidate metabolites were identified out in the discovery study, namely kynurenic acid, N-α-acetylarginine, 6-hydroxymelatonin, sphinganine, ceramide, sphingosine-1P, spermidine, and glycine. These metabolites exist in sphingolipid, glutathione, and tryptophan metabolic pathways. In the second-stage study, five candidate metabolites were validated, including kynurenic acid, N-α-acetylarginine, sphinganine, spermidine, and sphingosine-1P. Except for spermidine, all substances exhibited low expression in the case group compared with the external control group, and the difference in levels of sphinganine, spermidine, and sphingosine-1P was statistically significant. Conclusion The direction of change of levels of sphinganine, spermidine, and sphingosine-1P in the two-stage study cohorts was completely consistent, and the differences were statistically significant. Therefore, these substances can be used as potential biomarkers of KBD. Furthermore, these results raise the possibility that sphingolipid metabolic pathways may be closely related to KBD.
Adolescent ; Biomarkers/blood* ; Child ; China ; Cohort Studies ; Female ; Humans ; Kashin-Beck Disease/blood* ; Male ; Metabolic Networks and Pathways ; Metabolome

Objective This study was designed to determine the methylation profile of four CpGs and the genotypes of two CpG-SNPs located in promoter region of DIO2 in patients with Kashin-Beck disease (KBD). We also analyzed the interaction between the CpGs methylations and CpG-SNPs. Methods Whole blood specimens were collected from 16 KBD patients and 16 healthy subjects. Four CpGs and two CpG-SNPs in the promoter regions of DIO2 were detected using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The CpGs methylation levels were compared between samples from KBD patients and healthy subjects. The methylation levels were also analyzed in KBD patients with different CpG-SNP genotypes. Results The mRNA expression of DIO2 in whole blood of KBD patients was significnatly lower than in healthy controls (P <0.05). The methylation levels of DIO2-1_CpG_3 in KBD patients were significantly higher than those in healthy controls (P <0.05). The methylation levels of four CpGs were not significantly different between KBD patients and healthy controls. The methylation level of DIO2-1_CpG_3 in the promoter region of DIO2 in KBD patients with GA/AA genotype was significantly higher than that of KBD patients with GG genotype (P <0.05). Conclusion The methylation level of DIO2 increases in KBD patients. Similar trends exist in KBD carriers of variant genotypes of CpG-SNPs DIO2 rs955849187.
Case-Control Studies ; Humans ; Iodide Peroxidase/genetics* ; Kashin-Beck Disease/genetics* ; Methylation ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic

OBJECTIVETo study the association between single nucleotide polymorphisms of thioredoxin reductase-2 (TrxR2) gene and the susceptibility to Kashin-Beck disease (KBD).

METHODSPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the genotype frequencies of rs5748469 in TrxR2 gene in 84 KBD patients and 109 healthy control subjects.

RESULTSThe genotype frequencies of A/A, A/C, and C/C in the KBD patients were 83.33%, 15.48% and 1.19%, as compared with the frequencies of 74.31%, 25.69%, and 0.00% in the healthy control, respectively, showing no significant difference in the single nucleotide polymorphisms of TrxR2 gene between the two groups (P=0.13).

CONCLUSIONNo obvious correlation can be found between rs5748469 polymorphisms in TrxR2 gene and the susceptibility to KBD.

Adult ; Alleles ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Kashin-Beck Disease ; genetics ; Male ; Middle Aged ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Thioredoxin Reductase 2 ; genetics

OBJECTIVETo identify the genetic susceptibility to Kashin-Beck disease (KBD) and explore the interaction between low selenium (Se) and the susceptibility gene loci in KBD.

METHODSThe DNA samples collected from 23 KBD nuclear families were analyzed using PCR and GeneScan Analysis 3.7 and Genotyper3.7 software. The haplotype relative risk (HRR) and transmission disequilibrium test (TDT) were used to test the data of the genotypes. The serum selenium (Se) concentration was measured by atomic fluorescence spectrometry, and the interaction between low Se and the susceptibility loci was calculated using a binary logistic regression.

RESULTSIn the 23 nuclear families, the alleles of D2S151 (248 bp), D2S305 (320 bp), and D11S4094 (194 bp) showed significant correlation to KBD (P<0.05). Serum Se concentrations in the studied individuals was 0.037 µg/ml. No significant statistical interaction was observed between low Se exposure and the susceptibility loci (P>0.05).

CONCLUSIONThe polymorphisms in the STR loci D2S305, D2S151, and D11S4094 or the polymorphism loci near them might been related to KBD susceptibility. Low Se exposure shows no significant interaction with the susceptibility loci.

Adolescent ; Adult ; Alleles ; Child ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Kashin-Beck Disease ; blood ; etiology ; genetics ; Male ; Microsatellite Repeats ; Middle Aged ; Pedigree ; Selenium ; blood ; Young Adult

A case-control study was conducted to investigate associations between organophosphate pesticide (OP) exposure, aggression, impulsivity, and attempted suicide. The purpose of this study was to explore whether genomic polymorphisms in the alpha 1(XI) collagen gene (COL11A1) were associated with the risk and severity of Kashin-Beck disease (KBD). Twenty-two single nucleotide polymorphisms (SNPs) in COL11A1 were genotyped in 274 KBD cases and 249 healthy controls using the Sequenom MassARRAY system. The expression of type XI collagen (COL11A) in the knee articular cartilage of 22 KBD patients and 21 controls was analyzed by immunohistochemistry. Our results showed that the frequency distribution of genotypes of the rs2229783 polymorphism in COL11A1 was significantly different between the KBD and control groups (P = 0.0003). Moreover, the expression level of COL11A in cartilage was significantly lower in the KBD group than in the controls (t = 2.637, P = 0.02). However, no association was found between the rs2229783 and the severity of KBD, suggesting a role of COL11A1 in the susceptibility to but not the severity of KBD.
Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Collagen Type XI ; genetics ; Genetic Predisposition to Disease ; Genotype ; Humans ; Kashin-Beck Disease ; genetics ; Polymorphism, Single Nucleotide

Kashin-Beck disease (KBD) is an endemic degenerative osteoarthropathy of uncertain etiology. The aim of our study was to identify changes in C-telopeptide of type II collagen (CTX-II), pyridinoline (PYD), and deoxypyridinoline (DPD) among KBD patients. 54 KBD patients and 78 healthy controls were included this study. Urinary samples were collected and measured by ELISA. The median quantities of PYD, CTX-II, and DPD of KBD patients were 1107.73 ng/μmol.cre, 695.11 ng/μmol.cre, and 1342.34 pml/μmol.cre, while the median quantities of healthy controls were 805.59 ng/μmol.cre, 546.47 ng/μmol.cre, and 718.15 pml/μmol.cre, respectively. The differences between KBD patients and healthy controls were statistically significant (Z = 4.405, 3.653, and 3.724; P < 0.001). The higher levels of PYD, CTX-II, and DPD detected in KBD patients indicate that they could be used as biomarkers of KBD.
Adult ; Amino Acids ; urine ; Biomarkers ; urine ; China ; Collagen Type II ; urine ; Female ; Humans ; Kashin-Beck Disease ; diagnosis ; urine ; Male ; Middle Aged ; Peptide Fragments ; urine

This study aimed to evaluate the sensitivity and specificity of the new clinical diagnostic and classification criteria for Kashin-Beck disease (KBD) using six clinical markers: flexion of the distal part of fingers, deformed fingers, enlarged finger joints, shortened fingers, squat down, and dwarfism. One-third of the total population in Linyou County was sampled by stratified random sampling. The survey included baseline characteristics and clinical diagnoses, and the sensitivity and specificity of the new criteria was evaluated. We identified 3,459 KBD patients, of which 69 had early stage KBD, 1,952 had stage I, 1,132 had stage II, and 306 had stage III. A screening test classified enlarged finger joints as stage I KBD, with a sensitivity and specificity of 0.978 and 0.045, respectively. Shortened fingers were classified as stage II KBD, with a sensitivity and specificity of 0.969 and 0.844, respectively, and dwarfism was classified as stage III KBD with a sensitivity and specificity of 0.951 and 0.992, respectively. Serial screening test revealed that the new clinical classification of KBD classified stages I, II, and III KBD with sensitivities of 0.949, 0.945, and 0.925 and specificities of 0.967, 0.970, and 0.993, respectively. The screening tests revealed that enlarged finger joints, shortened fingers, and dwarfism were appropriate markers for the clinical diagnosis and classification of KBD with high sensitivity and specificity.
Adolescent ; Adult ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Kashin-Beck Disease ; classification ; diagnosis ; epidemiology ; pathology ; Male ; Middle Aged ; Young Adult