HLA-B*27/HLA-B*07 in combination with D6S273-134 allele is associated with increased susceptibility to juvenile
M Harjacek1, T Margetić, V Kerhin-Brkljacić
1Division of Pediatric Rheumatology/Immunology, Children's Hospital Zagreb, Croatia. miroslav.harjacek@zg.htnet.hr
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.
Patients And 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).
Conclusion:
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.
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