title: Polymorphisms of the IL-23R gene are associated with primary immune thrombocytopenia but not with the clinical outcome of pulsed high-dose dexamethasone therapy.
abstract: Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder that is characterized by decreased platelet count. The interleukin-23 receptor (IL-23R) has been identified as a susceptibility gene for the development of multiple autoimmune diseases. To investigate the possible association of IL-23R gene single-nucleotide polymorphisms (SNPs) with ITP and the association with the clinical outcome of pulsed high-dose dexamethasone (HD-DXM) therapy, four SNPs in the IL-23R gene, rs10889677, rs1884444, rs7517847, and rs11209032, were tested in a cohort of 75 ITP subjects and 81 controls by direct sequencing. IL-23R rs1884444 GT/TT variant genotypes were observed to be associated with significantly increased risk of ITP as compared with controls (GT/TT vs. GG: odds ratio (OR) 2.776, 95 % confidence intervals (CI) 1.086-7.090, p = 0.028). However, other three SNPs revealed no statistically significant differences between patients and controls (rs10889677 CA/AA vs. CC: OR 2.200, 95 % CI 0.727-6.661, p = 0.155; rs11209032 GA/AA vs. GG: OR 0.747, 95 % CI 0.379-1.472, p = 0.399; rs7517847 TG/GG vs. TT: OR 1.031, 95 % CI 0.544-1.956, p = 0.925). Furthermore, IL-23R SNPs revealed no association with clinical outcome of HD-DXM therapy. This study suggests that polymorphism in the IL-23R gene, rs1884444, indicates a significant association with susceptibility to ITP in a recessive genetic model but does not have association with the clinical outcome of HD-DXM therapy.
authors.affiliation: Department of Hematology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Zhan
authors.forename: Fanli
authors.initials: F
authors.lastname: Hua
authors.forename: Lili
authors.initials: L
authors.lastname: Ji
authors.forename: Weiguang
authors.initials: W
authors.lastname: Wang
authors.forename: Shanhua
authors.initials: S
authors.lastname: Zou
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002681:China / Q000453:epidemiology; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D018123:Receptors, Interleukin / Q000235:genetics* / Q000502:physiology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C515500:IL23R protein, human; D018123:Receptors, Interleukin; D003907:Dexamethasone