title: Signal transducer and activator of transcription 4 gene polymorphisms associated with rheumatoid arthritis in Northwestern Chinese Han population.
abstract: OBJECTIVE
  Signal transducer and activator of transcription 4 (STAT4) gene encode a transcriptional factor that transmits signals induced by several key cytokines which play important roles in the development of autoimmune diseases. Recently, several single nucleotide polymorphisms (SNPs) in STAT4 gene have been reported to be significantly associated with Rheumatoid arthritis (RA) in different ethnic populations. We undertook this study to investigate whether the association of STAT4 genetic polymorphisms with RA is present in Northwestern Chinese Han population.
  
  
  METHODS
  A case-control association study in individuals with RA (n=208) and healthy controls (n=312) was conducted. Four SNPs (rs7574865, rs8179673, rs10181656, rs11889341) in STAT4 gene were genotyped by using polymerase chain reaction followed by denaturing high-performance liquid chromatography (PCR-DHPLC) and DNA sequencing.
  
  
  RESULTS
  The genotype and allele distributions of four polymorphisms were significantly different in individuals with RA compared to controls, with SNP rs7574865 T allele and T/T genotype showing the most significant association with susceptibility to RA (uncorrected P=1×10(-4), OR=1.645, 95% CI=1.272-2.129; uncorrected P=4.8×10(-5), OR=3.111, 95% CI=1.777-5.447, respectively). Stratification studies showed that STAT4 gene polymorphisms were significantly associated with anti-cyclic citrullinated peptide (anti-CCP) positive subgroup in Northwestern Chinese Han population.
  
  
  CONCLUSIONS
  These findings strongly suggest that STAT4 genetic polymorphisms are associated with RA in Northwestern Chinese Han population, and support the hypothesis of STAT4 gene polymorphisms increasing the risk for RA across major populations.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, China.
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Liang
authors.forename: Hua
authors.initials: H
authors.lastname: Wu
authors.forename: Pei-Qiang
authors.initials: PQ
authors.lastname: Li
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Xie
authors.forename: Xi
authors.initials: X
authors.lastname: Shen
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Yang
authors.forename: Xuan
authors.initials: X
authors.lastname: Cheng
authors.forename: Li
authors.initials: L
authors.lastname: Liang
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000453:epidemiology* / Q000235:genetics*; D044466:Asian People; D001323:Autoantibodies / Q000032:analysis; D002681:China / Q000453:epidemiology; D004247:DNA / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012217:Rheumatoid Factor / Q000276:immunology; D050797:STAT4 Transcription Factor / Q000235:genetics*
chemical_list: D001323:Autoantibodies; D005819:Genetic Markers; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D004247:DNA; D012217:Rheumatoid Factor