A severe selenium deficiency was documented as well, but selenium statuswas not associated with the disease, suggesting that selenium deficiency alone could not explain the occurrence of KBD in the villages under study.An association with the gene Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 Beta (PPARGC1B) has been reported. This gene is a transcription factor and mutations in this gene would be expected to affect several other genes. Prevention
Prevention of Kashin–Beck disease has a long history. Intervention strategies were mostly based on one of the three major theories of its cause. Selenium supplementation, with or without additional antioxidant therapy (vitamin E and vitamin C) has been reported to be successful, but in other studies no significant decrease could be shown compared to a control group. Major drawbacks of selenium supplementation are logistic difficulties (including daily or weekly intake and drug supply), potential toxicity (in case of less well-controlled supplementation strategies), associated iodine deficiency (that should be corrected before selenium supplementation to prevent further deterioration of thyroid status) and low compliance. The latter was certainly the case in Tibet, where selenium supplementation has been implemented from 1987 to 1994 in areas of high endemicity. With the mycotoxin theory in mind, backing of grains before storage was proposed in Guangxi province, but results are not reported in international literature. Changing from grain source has been reported to be effective in Heilongjiang Province and North Korea.
T-2 toxin can cause lesions in hematopoietic, lymphoid, gastrointestinal, and cartilage tissues, especially in physeal cartilage. Fulvic acid present in drinking water damages cartilage cells. Selenium supplementation in selenium deficient areas has been shown to prevent this disease. However, selenium supplementation in some areas showed no significant effect, meaning that deficiency of selenium may not be the dominant cause in KBD. Recently a significant association between SNP rs6910140 of COL9A1 and Kashin–Beck disease was discovered genetically, suggesting a role of COL9A1 in the development of Kashin–Beck disease. Cause
The cause of KBD remains controversial. Studies of the pathogenesis and risk factors of KBD have proposed selenium deficiency, inorganic (e.g. manganese, phosphate) and organic matter (humic and fulvic acids) in drinking water, and fungi on self-produced storage grain (Alternaria sp., Fusarium sp.) producing trichotecene (T2) mycotoxins. Most authors accept that the cause of KBD is multifactorial, selenium deficiency being the underlying factor that predisposes the target cells (chondrocytes) to oxidative stress from free-radical carriers, such as mycotoxins in storage grain and fulvic acid in drinking water. In Tibet, epidemiological studies carried out in 1995–1996 by MSF and coll. showed that KBD was associated with iodine deficiency and with fungal contamination of barley grains by Alternaria sp., Trichotecium sp., Cladosporium sp. and Drechslera sp. Indications existed as well with respect to the role of organic matters in drinking water.