title: Investigation of T-cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) polymorphisms in essential thrombocythaemia (ET).
abstract: OBJECTIVE
  T-cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) is preferentially expressed on terminally differentiated Th1 cells and inhibits their IFN-γ production. It has been reported that chronic inflammation may be an important driving force for myeloproliferative neoplasms (MPNs). Therefore, we hypothesized that as an important inflammation regulator, TIM-3 may be involved in essential thrombocythaemia (ET). The goal of this study was to investigate whether the -1516G > T, -574G > T and +4259T > G single-nucleotide polymorphisms (SNPs) within the TIM-3 gene contribute to the genetic susceptibility of individuals to ET.
  
  
  METHODS
  Genotyping of the TIM-3 -1516G > T, -574G > T and + 4259T > G SNPs was performed in 175 patients with ET and in 151 controls via a polymerase chain reaction-restriction fragment length polymorphism assay. We also investigated the relationships between the genotypes of each SNP and the risk factors of ET such as routine blood indexes, age and JAK2 V617F mutation.
  
  
  RESULTS
  The genotype and allele frequencies of the -1516G > T SNP (p = 0.016 and 0.019, respectively), the -574G > T SNP (p = 0.035 and 0.038, respectively) and the +4259T > G SNP (p = 0.036 and 0.038, respectively) of the ET patients and the controls were significantly different. A haplotype analysis found that the GGT and TGT haplotypes had significantly different distributions between ET and controls (p = 0.041 and 0.041, respectively). However, no significant differences were detected between the genotypes of all SNPs and routine blood indexes, age and JAK2V617F mutation.
  
  
  CONCLUSIONS
  The -1516G > T, -574G > T and +4259T > G SNPs within TIM-3 gene might play an important role as a genetic risk factor in the pathogenesis of ET.
authors.affiliation: a Department of Clinical Laboratory , Shandong Provincial Hospital Affiliated to Shandong University , Jinan , Shandong , China.
authors.forename: Fuyan
authors.initials: F
authors.lastname: Han
authors.affiliation: b Department of Respiration , Shandong Provincial Qianfoshan Hospital Affiliated to Shandong University , Jinan , Shandong , China.
authors.forename: Guanghai
authors.initials: G
authors.lastname: Wang
authors.affiliation: a Department of Clinical Laboratory , Shandong Provincial Hospital Affiliated to Shandong University , Jinan , Shandong , China.
authors.forename: Yuantang
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Department of Clinical Laboratory , Shandong Provincial Hospital Affiliated to Shandong University , Jinan , Shandong , China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Tian
authors.affiliation: a Department of Clinical Laboratory , Shandong Provincial Hospital Affiliated to Shandong University , Jinan , Shandong , China.
authors.forename: Zhenfang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: a Department of Clinical Laboratory , Shandong Provincial Hospital Affiliated to Shandong University , Jinan , Shandong , China.
authors.forename: Shiqing
authors.initials: S
authors.lastname: Cheng
authors.affiliation: a Department of Clinical Laboratory , Shandong Provincial Hospital Affiliated to Shandong University , Jinan , Shandong , China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: a Department of Clinical Laboratory , Shandong Provincial Hospital Affiliated to Shandong University , Jinan , Shandong , China.
authors.forename: Teng
authors.initials: T
authors.lastname: Qu
authors.affiliation: c Department of Pathology , The Second Hospital of Shandong University , Jinan , Shandong , China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.affiliation: a Department of Clinical Laboratory , Shandong Provincial Hospital Affiliated to Shandong University , Jinan , Shandong , China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: a Department of Clinical Laboratory , Shandong Provincial Hospital Affiliated to Shandong University , Jinan , Shandong , China.
authors.forename: Bingchang
authors.initials: B
authors.lastname: Zhang
authors.affiliation: a Department of Clinical Laboratory , Shandong Provincial Hospital Affiliated to Shandong University , Jinan , Shandong , China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ju
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000235:genetics*; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013920:Thrombocythemia, Essential / Q000175:diagnosis / Q000235:genetics*
chemical_list: C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D053614:Janus Kinase 2
keywords: JAK2 V617F; PCR-RFLP; T-cell immunoglobulin- and mucin-domain-containing molecule-3; age; essential thrombocythaemia; polymorphism; risk factors; routine blood indexes