title: Association of aplastic anemia and FoxP3 gene polymorphisms in Koreans.
abstract: OBJECTIVE
  Aplastic anemia (AA) is characterized by pancytopenia and bone marrow failure, and most acquired AA is an immune-mediated disorder. Regulatory T cells (Tregs) suppressing autoreactive T cells were decreased in AA patients. FoxP3 is a major regulator for the development and function of Tregs. Polymorphism in FoxP3 was shown to be associated with various autoimmune diseases, however, has not yet been studied in AA. In this study, we examined the association between FoxP3 polymorphisms and AA in Korean patients.
  
  
  METHODS
  The study population consisted of 94 patients diagnosed by bone marrow examination in Seoul National University Hospital (SNUH) during 1997-2012 and 195 healthy controls. FoxP3 polymorphisms (rs5902434 del/ATT, rs3761548 C/A, rs3761549 C/T, rs2232365 A/G) were analyzed by PCR-sequencing method. We analyzed differences of genotype and allele frequencies between patients and controls. We also compared differences of genotype and allele frequencies between responder and non-responder in patients treated with immunosuppressive therapy (IST). For the statistical analysis, the chi-square test and Fisher's exact test were used and P < 0.05 was regarded as statistically significant.
  
  
  RESULTS
  There was no signiﬁcant difference in the genotype frequencies of FoxP3 polymorphisms between patients and controls. With regards to the allele frequencies, rs3761548 C allele was significantly higher in AA patients than in controls (87.4% vs. 79.7%, P = 0.047). In patients treated with IST, rs3761549 C allele was significantly higher in non-responder patients than in responders (89.6% vs. 66.7%, P = 0.036) and female rs3761549 C/C genotype carriers were associated with greater risk for non-response to IST (84.2% vs. 16.7%, P = 0.006).
  
  
  CONCLUSIONS
  Polymorphisms in rs3761548 and rs3761549 of FoxP3 in our population were associated with disease susceptibility and response for IST, respectively. This study suggests an association between FoxP3 polymorphisms and AA in Korean patients and will be useful in further understanding the genetic basis of disease susceptibility and response to IST in AA patients.
authors.affiliation: a Department of Laboratory Medicine , Seoul National University College of Medicine , Seoul , Korea.|b Department of Laboratory Medicine , Seoul Medical Center , Seoul , Korea.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: In
authors.affiliation: a Department of Laboratory Medicine , Seoul National University College of Medicine , Seoul , Korea.
authors.forename: Nuri
authors.initials: N
authors.lastname: Lee
authors.affiliation: a Department of Laboratory Medicine , Seoul National University College of Medicine , Seoul , Korea.|c Department of Laboratory Medicine , Seoul National University Boramae Medical Center , Seoul , Korea.
authors.forename: Eun Youn
authors.initials: EY
authors.lastname: Roh
authors.affiliation: a Department of Laboratory Medicine , Seoul National University College of Medicine , Seoul , Korea.|c Department of Laboratory Medicine , Seoul National University Boramae Medical Center , Seoul , Korea.
authors.forename: Sue
authors.initials: S
authors.lastname: Shin
authors.affiliation: a Department of Laboratory Medicine , Seoul National University College of Medicine , Seoul , Korea.
authors.forename: Kyoung Un
authors.initials: KU
authors.lastname: Park
authors.affiliation: a Department of Laboratory Medicine , Seoul National University College of Medicine , Seoul , Korea.|d Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine , Medical Research Center, Seoul National University , Seoul , Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Song
mesh_terms: D000328:Adult; D000483:Alleles; D000741:Anemia, Aplastic / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D016022:Case-Control Studies; D003131:Combined Modality Therapy; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006684:HLA-DR Antigens
keywords: Aplastic anemia; FoxP3; immunosuppressive therapy; regulatory T cell; single nucleotide polymorphism