GWAS of Serum Antibodies to Microbial Biomarker Species of Periodontitis

Serum antibody levels against microbial biomarkers of periodontitis, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis , are associated especially with the presence of these species in the oral cavity. We investigated the genetic basis of host antibody responses against these species through a genome-wide association study (GWAS) to identify the genetic determinants of this immune reactivity. Serum immunoglobulin A (IgA) and immunoglobulin G (IgG) antibody levels against A. actinomycetemcomitans and P. gingivalis were determined using multiserotype enzyme-linked immunosorbent assay in 3,719 participants from 4 Finnish cohort studies: FinnTwin, Parogene, FINRISK97, and Health-2000. The associations of genetic polymorphisms and imputed human leukocyte antigen (HLA) alleles with antibody levels were investigated. All antibody levels presented significant increasing trends with periodontitis stage and grade. A. actinomycetemcomitans IgG displayed association with single nucleotide polymorphisms (SNPs) in chromosome 6 with lead SNP rs574581129 (near HLA-DRB1 , P = 3.6 × 10 −8 ) and P. gingivalis IgG in chromosome 14 with lead SNP rs146761521 (near NUBPL , 5.5 × 10 −8 ). In addition, all antibody levels presented suggestive associations with several loci. Detailed HLA analyses revealed that A. actinomycetemcomitans IgG was associated with DQA1*01:01, DQB1*05:01, and DRB1*01:01 and P. gingivalis IgG with HLA-A*02:01 alleles. Both IgA and IgG antibody levels against microbial biomarker species of periodontitis increase with periodontitis stage and grade, but genetic variation is also a significant predictor. Specific alleles within the HLA region may influence antibody responses to A. actinomycetemcomitans and P. gingivalis , highlighting potential genetic contributions to the immunological mechanisms underlying periodontitis.