Stein J, Reichert S, Gautsch A, Machulla H K G
Interbranch HLA Laboratory/Department GHATT, Institute of Medical Immunology, Martin Luther University, Halle, Germany.
J Periodontal Res. 2003 Oct;38(5):508-17. doi: 10.1034/j.1600-0765.2003.00683.x.
Human leukocyte antigens (HLA)/alleles have been considered as risk factors for periodontal disease. However, data from HLA associations is not consistent. Diversity of HLA antigen combinations and en bloc inherited HLA alleles (haplotypes), as known in systemic diseases, can be variable factors in disease association. Therefore, the aim of this study was to investigate the incidence of HLA homozygosities, heterozygosities and estimated haplotypes in German Caucasian groups with generalized aggressive (N = 50) and chronic (N = 102) periodontitis in comparison to control probands without periodontitis (N = 102).
HLA-A, -B, -Cw, -DRB1, -DRB3/4/5, -DQB1 typing was carried out using both serologic (microlymphocytotoxicity test) and genomic (PCR-SSP: PCR with sequence specific primers) techniques. Frequencies of all homozygosities, heterozygosities and haplotypes were determined in all patients and controls.
In both patient groups, associations to HLA homozygosities and heterozygosities were found. Most striking was the significantly lower frequency of HLA-DRBblank* homozygosity (non-DRB3*/DRB4*/DRB5*) in chronic periodontitis (p < 0.05), whereas HLA-DRB115 : DRB5(DR51) : DQB106 showed a slightly higher homozygosity rate in all patients. As the combination HLA-A02,A03 was significantly decreased in aggressive periodontitis (p < 0.05), HLA-A01,A03 heterozygosity was significantly lowered in chronic periodontitis (p < 0.05). Among others, the known positive associations for HLA-A68/69 (A28) and HLA-DRB104 were confirmed by the haplotypes HLA-A68/69 : Cw07 : B18 in aggressive periodontitis (p < 0.05) and HLA-Cw08 : B14 : DRB1*04 in chronic periodontitis (p < 0.05).
The present study elucidates the variety of HLA associations and therefore the difficulty to assign single HLA markers to periodontal disease. Susceptibility/resistance of both aggressive and chronic periodontitis may rather be influenced by particular HLA marker combinations. Associated HLA haplotypes may be of further importance for unknown gene loci representing a part of the genetic background for periodontitis. The different associations in aggressive and chronic periodontitis indicate different susceptibility/resistance factors for both diseases.