title: Genetic variants in the HLA-DRB1 gene are associated with Kashin-Beck disease in the Tibetan population.
abstract: OBJECTIVE
  To investigate the association between variants in the HLA-DRB1 gene and Kashin-Beck disease (KBD), as well as associations of selenium and iodine deficiencies with KBD in a Tibetan population.
  
  
  METHODS
  Fourteen single-nucleotide polymorphisms (SNPs) were genotyped around the HLA-DRB1 gene, and HLA-DRB1 allele genotyping was performed in a discovery cohort, composed of 605 patients with KBD and 393 control subjects, and/or a replication cohort, composed of 290 patients with KBD and 295 controls. Plasma concentrations of selenium and iodine were measured and compared by t-test in 299 patients with KBD and 280 controls from the same villages.
  
  
  RESULTS
  Four SNPs (rs6457617, rs6457620, rs9275295, and rs7745040) in the HLA-DRB1 gene locus were significantly associated with KBD in both the discovery cohort and replication cohort (combined cohort odds ratios [ORs] 1.307-1.402, P = 0.0039-0.0006). The protective haplotype GTCC and the risk haplotype ACGT, each generated by the 4 SNPs, showed a significant association with KBD (for GTCC, OR 0.77, P = 0.0031; for ACGT, OR 1.40, P = 0.0014). HLA-DRB1 allele genotyping revealed that the frequencies of HLA-DRB1*08 and *11 were significantly different between patients with KBD and controls (for HLA-DRB1*08, OR 0.731, P = 0.00564; for HLA-DRB1*11, OR 0.489, P = 0.000395). Moreover, plasma concentrations of selenium and iodine were significantly different between patients with KBD and controls from the same villages (P = 0.0013 and P = 1.84 × 10(-12) , respectively).
  
  
  CONCLUSIONS
  These findings, obtained in plasma samples from Tibetan patients with KBD and healthy control subjects from the same regions, confirm the role of selenium and iodine deficiencies in the development of KBD. Moreover, genetic variants in the HLA-DRB1 gene significantly increase the susceptibility to KBD in this population.
authors: Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Sichuan, China.
authors: Yi
authors: Y
authors: Shi
authors: Fang
authors: F
authors: Lu
authors: Xin
authors: X
authors: Liu
authors: Yao
authors: Y
authors: Wang
authors: Lulin
authors: L
authors: Huang
authors: Xiaoqi
authors: X
authors: Liu
authors: Wubin
authors: W
authors: Long
authors: Bo
authors: B
authors: Lv
authors: Kun
authors: K
authors: Zhang
authors: Shi
authors: S
authors: Ma
authors: He
authors: H
authors: Lin
authors: Jing
authors: J
authors: Cheng
authors: Bin
authors: B
authors: Zhou
authors: Mei
authors: M
authors: Hu
authors: Jiayun
authors: J
authors: Deng
authors: Jianxin
authors: J
authors: Zhu
authors: Peng
authors: P
authors: Hao
authors: Xiao
authors: X
authors: Yang
authors: Mingcai
authors: M
authors: Zeng
authors: Xiaoquan
authors: X
authors: Wang
authors: Sikui
authors: S
authors: Shen
authors: Zhenglin
authors: Z
authors: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007455:Iodine / Q000097:blood; D057767:Kashin-Beck Disease / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012643:Selenium / Q000097:blood; D018609:Tibet
chemical_list: D059811:HLA-DRB1 Chains; D007455:Iodine; D012643:Selenium