The genetics of Kashin-Beck disease in Tibet

http://www.ncbi.nlm.nih.gov/pubmed/21739420

Arthritis Rheum. 2011 Jul 7. doi: 10.1002/art.30526. [Epub ahead of print]
Genetic variants in HLA-DRB1 gene are associated with Kashin-Beck disease in the Tibetan population.
Shi Y, Lu F, Liu X, Wang Y, Huang L, Liu X, Long W, Lv B, Zhang K, Ma S, Lin H, Cheng J, Zhou B, Hu M, Deng J, Zhu J, Hao P, Yang X, Zeng M, Wang X, Yang Z.
Source
Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Sichuan, China; Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Sichuan, China.

Abstract
OBJECTIVE:
To investigate the association between variants in HLA-DRB1 gene and Kashin-Beck disease (KBD) and selenium and iodine deficiencies in KBD in a Tibetan population.

METHODS:
We genotyped 14 polymorphisms around HLA-DRB1 gene and performed HLA-DRB1 allele genotyping in the discovery cohort composed of 605 patients and 393 controls and/or the replication cohort composed of 290 patients and 295 controls. Plasma selenium and iodine concentrations of 299 KBD patients and 280 controls from the same villages were measured and compared by t test.

RESULTS:
We found four SNPs (rs6457617, rs6457620, rs9275295, and rs7745040) in the HLA-DRB1 gene locus that were significantly associated with KBD in both cohorts with combined P values from 0.0039 to 0.0006 (OR: from 1.307 to 1.402). The protective haplotype GTCC generated by the four SNPs showed significant association with KBD (P=0.0031, OR=0.77). The risk haplotype ACGT generated by the four SNPs showed significant association with KBD (P=0.0014, OR=1.40). In the HLA-DRB1 allele genotyping, the frequencies of HLA-DRB1*08 and *11 showed significant differences between KBD cases and controls (HLA-DRB1*08: OR=0.731, P=0.00564; HLA-DRB1*11: OR=0.489, P=0.000395). We also found that plasma selenium and iodine concentrations were significantly different between KBD patients and controls from the same villages (P=0.0013 and P=1.82x10(-12) , respectively).

CONCLUSION:
We confirmed the role of the selenium and iodine deficiencies in the development of KBD, using, for the first time, plasma samples of the KBD patients and controls from the same villages. We established that genetic variants in the HLA-DRB1 gene significantly increase susceptibility to KBD.

Copyright © 2011 by the American College of Rheumatology.