title: Tim-3 polymorphism downregulates gene expression and is involved in the susceptibility to ankylosing spondylitis.
abstract: Ankylosing spondylitis (AS) is a chronic inflammatory disorder primarily affecting the sacroiliac joints and the spine. T-cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) has been established as a negative regulatory molecule that plays a critical role in controlling inflammation. Studies have shown that polymorphisms in TIM-3 gene may be associated with inflammatory diseases. The current study investigated the association between polymorphisms in the TIM-3 gene and susceptibility to AS, and it examined the effects of these polymorphisms on gene expression. Two polymorphisms in TIM-3 -574G/T and +4259T/G polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism in 282 AS patients and 298 healthy controls. Results showed that frequency of the TIM-3 -574GT genotype was significantly increased in cases than in controls (Odd ratio [OR]=2.50, 95% confidence interval [CI]: 1.39-4.48, p=0.002). Similarly, TIM-3 -574T allele revealed a positive association with the disease (OR=2.39, p=0.002). The TIM-3 +4259T/G polymorphism did not show any correlation with AS. We further evaluated TIM-3 mRNA and protein levels in CD4(+) T cells, CD8(+) T cells, and monocytes from subjects carrying different TIM-3 genotypes. Results revealed that subjects carrying polymorphic -574GT genotype had significantly lower TIM-3 mRNA and protein levels in CD4(+) T cells, CD8(+) T cells, and monocytes than those with wild-type GG genotype. These data suggest that TIM-3 polymorphism is associated with increased susceptibility to AS possibly by downregulating gene expression.
authors.affiliation: 1 Department of Orthopedic Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine , Shanghai, China .
authors.forename: Mingfei
authors.initials: M
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Ji
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Cheng
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
authors.forename: Junjie
authors.initials: J
authors.lastname: Zhou
authors.forename: Chengfu
authors.initials: C
authors.lastname: Cao
authors.forename: Qunfeng
authors.initials: Q
authors.lastname: Guo
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D016022:Case-Control Studies; D002681:China; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D009000:Monocytes / Q000166:cytology; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012446:Sacroiliac Joint / Q000473:pathology; D013131:Spine / Q000473:pathology; D013167:Spondylitis, Ankylosing / Q000235:genetics*
chemical_list: C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins