title: HLA-B*27/HLA-B*07 in combination with D6S273-134 allele is associated with increased susceptibility to juvenile spondyloarthropathies.
abstract: OBJECTIVE
  Juvenile spondylarthropathies (jSpA) are polygenic and the clustering of disease in families is caused mainly by genetic factors. Our aim was to look for possible associations of other HLA-A and B specificities, MICA and D6S273 microsatellite polymorphisms that might play a role in determining the susceptibility to jSpA.
  
  
  METHODS
  jSpA were diagnosed in 74 Croatian children, and 169 healthy unrelated individuals served as the control group. HLA class I (A, B) typing of all individuals was performed, and HLA-B7 and HLA-B27 positive subjects were subtyped by PCR-SSP method. MICA and D6S273 microsatellites alleles were analyzed by electrophoresis in an automated sequencer.
  
  
  RESULTS
  We identified 26 HLA-B*07 and 31 HLA-B*27 positive patients with jSpA. DNA subtyping of HLA-B*27 specificity demonstrated only two subtypes, B*2702 (19.35%) and B*2705 (80.65%), among jSpA patients. Subtyping analysis of HLA-B*07 gene showed presence of only one subtype, B*0702. The OR for HLA-B*07 was 2.61, while the highest OR for a single HLA specificity was found for HLA-B*27 (OR=5.60). The HLA-B*07/B*27 combination found in six children showed higher risk (OR=14.82), but the combination of specificities: HLA-B*07/HLA-B*27, and D6S273-134 allele demonstrated the highest risk (OR=26.83). The association with D6S273-134 allele was not a result of the linkage disequilibrium with HLA-B*27 specificity (LD=-0.5).
  
  
  CONCLUSIONS
  Our findings provide evidence that HLA-B*27/HLA-B*07 in combination with D6S273-134 allele is associated with increased susceptibility to jSpA in Croatian children.
authors.affiliation: Division of Pediatric Rheumatology/Immunology, Children's Hospital Zagreb, Croatia. miroslav.harjacek@zg.htnet.hr
authors.forename: M
authors.initials: M
authors.lastname: Harjacek
authors.forename: T
authors.initials: T
authors.lastname: Margetić
authors.forename: V
authors.initials: V
authors.lastname: Kerhin-Brkljacić
authors.forename: N
authors.initials: N
authors.lastname: Martinez
authors.forename: Z
authors.initials: Z
authors.lastname: Grubić
mesh_terms: D000293:Adolescent; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D017523:Croatia; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D015796:HLA-B27 Antigen / Q000235:genetics*; D015793:HLA-B7 Antigen; D006239:Haplotypes / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D025242:Spondylarthropathies / Q000208:ethnology / Q000235:genetics*
chemical_list: D015235:HLA-B Antigens; C425023:HLA-B*07 antigen; D015796:HLA-B27 Antigen; D015793:HLA-B7 Antigen; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A