Genetic and heritable risk factors in periodontal disease
The purpose of this paper is to review the emerging area in periodontology aimed at defining and measuring host genetic risk factors for disease. Generalized prepubertal periodontitis patients are often beset with functionally abnormal PMN of neutrophils. There are two types of leukocyte adhesion deficiencies that can impair the recruitment of neutrophils and monocytes. There is the LAD type I wherein the 8-subunit of the MAC-1, FLA-1, and pl50,95 glycoprotein family is deficient. This deficiency appears to be transmitted by recessive genes. This family of molecules is present on granulocyte and monocytes, and mediates cell adherence to endothelium and complement binding. Only homozygotes appear to be at risk for developing GPP. The LAD type II is the absence of the Sialyl-Lewis-Xligand, which is normally present on the surface of neutrophils and binds to selecting expressed by endothelial cells. Consanguinity between parents of the affected children implicates the role of recessive genes in LAD. Other reports cite children of parents that were blood relatives that displayed GPP and JP and yet displayed normal neutrophil adherence, chemotaxis, and phagocytosis. These cases were not tested for monocyte functions. This again shows parental consanguinity playing a role in recessive genes, although other factors may be involved other than inherited neutrophil deficiencies for GPP. GPP shows a strong genetic basis for the disease as evidenced by the finding of GPP in genetic disorders such as Chediak-Higashi syndrome, Papillon-Lefevre syndrome, and Ehlers-Danlos syndrome typeVIII, to name a few.
Juvenile periodontitis shows a familial pattern and may result from the effects of genetic or environmental factors shared by family members. Studies have shown that the transmission of A.a. maybe the cause of the familial aggregation of JP. There are also several studies that suggest JP may be transmitted as an autosomal recessive rather than an X-linked disorder. It is apparent that JP is composed of multiple subforms and it is possible that each of these have different genetic and environmental risk factors. While neutrophil chemotactic defects and exposure to A.a. are frequently noted in JP patients, neither factor fits a pattern to suggest a causal relationship. Several independent investigators have found a statistically significant association between the HLA-A9 antigen and JP and RPP. The relative risk of early-onset periodontal disease in subjects with the HLA-A9 antigen is two to three times greater than in subjects lacking the antigen. Serum antibodies to one or more periodontal bacteria are generally elevated in patients with periodontal disease. Immune response genes within the major histocompatibility complex, which regulate T-cell-dependent immune response, appear to interact with gram-negative-linked genes to determine levels of serum antibodies of different isotopes and specificities . [M. C . R. ]
Michalowicz, B.S., J Periodont, 65:479, 1994