Association between T-Cell Immunoglobulin and Mucin Domain 3 (TIM-3) Genetic Polymorphisms and Susceptibility to Autoimmune Diseases. 2019

Rui Zhang, and He Li, and Linfu Bai, and Jun Duan
a Department of Respiratory Medicine , The First Affiliated Hospital of Chongqing Medical University , Chongqing , China.

Background: Polymorphisms in T-cell immunoglobulin and mucin domain 3 (TIM-3) gene have been implicated in susceptibility to autoimmune diseases (ADs) with inconsistent results. The aim of this study was to perform meta-analyses for clarifying the relationship between them. Methods: All relevant case-control studies were searched in PubMed, Embase, Wanfang, and China National Knowledge Infrastructure. Meta-analysis was conducted in the dominant and allelic models, and checked for heterogeneity and publication bias. The Odds ratio (OR) and 95% confidence interval (CI) was used to assess the strength of the associations. Results: Seventeen studies with four TIM-3 polymorphisms (+4259A>C, -574G>T, -1516G>T, and -1541C>T) were identified, involving 3,399 cases and 3,911 controls. TIM-3 -1516G>T polymorphism showed significant associations with ADs risk among Chinese; however, the significant finding was unstable in sensitivity analysis. In the overall population, TIM-3 + 4259A>C polymorphism demonstrated stable significant associations with ADs risk in the dominant (OR = 1.57, 95%CI = 1.13-2.18, P = 0.007) and allelic (OR = 1.51, 95%CI = 1.10-2.08, P = 0.01) models, and with rheumatoid arthritis (RA) risk in the dominant (OR = 2.09, 95%CI = 1.60-2.73, P < 0.00001) and allelic (OR = 1.95, 95%CI = 1.51-2.51, P < 0.00001) models. Cumulative meta-analyses confirmed that these significant results were robust. Concerning TIM-3 -574 G > T or -1541C>T polymorphism, no significant associations were detected. Conclusion: These findings reveal that TIM-3 + 4259A>C might be a potential susceptible predictor of ADs and especially RA. Further functional and clinical investigation between these diseases and TIM-3 polymorphisms is warranted.

UI MeSH Term Description Entries
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D002681 China A country spanning from central Asia to the Pacific Ocean. Inner Mongolia,Manchuria,People's Republic of China,Sinkiang,Mainland China
D005787 Gene Frequency The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION. Allele Frequency,Genetic Equilibrium,Equilibrium, Genetic,Allele Frequencies,Frequencies, Allele,Frequencies, Gene,Frequency, Allele,Frequency, Gene,Gene Frequencies
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072597 Hepatitis A Virus Cellular Receptor 2 An Ig domain-containing membrane receptor that is expressed by TH1 CELLS. It regulates the activation of MACROPHAGES and inhibits TH1-mediated auto- and alloimmune responses to promote IMMUNE TOLERANCE. CD366 Antigen,HAVCR2 Protein,T-Cell Immunoglobulin Mucin Receptor 3,T-Cell Immunoglobulin and Mucin Domain-Containing Protein 3,TIMD3 Protein,Antigen, CD366,T Cell Immunoglobulin Mucin Receptor 3,T Cell Immunoglobulin and Mucin Domain Containing Protein 3
D001172 Arthritis, Rheumatoid A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated. Rheumatoid Arthritis
D001327 Autoimmune Diseases Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides. Autoimmune Disease,Disease, Autoimmune,Diseases, Autoimmune
D012307 Risk Factors An aspect of personal behavior or lifestyle, environmental exposure, inborn or inherited characteristic, which, based on epidemiological evidence, is known to be associated with a health-related condition considered important to prevent. Health Correlates,Risk Factor Scores,Risk Scores,Social Risk Factors,Population at Risk,Populations at Risk,Correlates, Health,Factor, Risk,Factor, Social Risk,Factors, Social Risk,Risk Factor,Risk Factor Score,Risk Factor, Social,Risk Factors, Social,Risk Score,Score, Risk,Score, Risk Factor,Social Risk Factor
D016022 Case-Control Studies Comparisons that start with the identification of persons with the disease or outcome of interest and a control (comparison, referent) group without the disease or outcome of interest. The relationship of an attribute is examined by comparing both groups with regard to the frequency or levels of outcome over time. Case-Base Studies,Case-Comparison Studies,Case-Referent Studies,Matched Case-Control Studies,Nested Case-Control Studies,Case Control Studies,Case-Compeer Studies,Case-Referrent Studies,Case Base Studies,Case Comparison Studies,Case Control Study,Case Referent Studies,Case Referrent Studies,Case-Comparison Study,Case-Control Studies, Matched,Case-Control Studies, Nested,Case-Control Study,Case-Control Study, Matched,Case-Control Study, Nested,Case-Referent Study,Case-Referrent Study,Matched Case Control Studies,Matched Case-Control Study,Nested Case Control Studies,Nested Case-Control Study,Studies, Case Control,Studies, Case-Base,Studies, Case-Comparison,Studies, Case-Compeer,Studies, Case-Control,Studies, Case-Referent,Studies, Case-Referrent,Studies, Matched Case-Control,Studies, Nested Case-Control,Study, Case Control,Study, Case-Comparison,Study, Case-Control,Study, Case-Referent,Study, Case-Referrent,Study, Matched Case-Control,Study, Nested Case-Control

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