HLA-B*27/HLA-B*07 in combination with D6S273-134 allele is associated with increased susceptibility to juvenile spondyloarthropathies.
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.
Harjacek
M
M
Division of Pediatric Rheumatology/Immunology, Children's Hospital Zagreb, Croatia. miroslav.harjacek@zg.htnet.hr
Margetić
T
T
Kerhin-Brkljacić
V
V
Martinez
N
N
Grubić
Z
Z
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*
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