The combined genotypes of stimulatory and inhibitory Fc gamma receptors associated with systemic lupus erythematosus and periodontitis in Japanese adults.
BACKGROUND
The pathobiology of systemic lupus erythematosus (SLE) is similar to that of periodontitis in that the immunoglobulin G Fc receptor (FcgammaR) and proinflammatory cytokines play an important role. Genetic variations of FcgammaR and interleukin (IL)-1 are associated with susceptibility to both diseases. Therefore, we evaluated whether the combination of FcgammaR or IL-1 polymorphic genes represents a common risk factor for SLE and periodontitis.


METHODS
The study population consisted of Japanese adults with SLE and periodontitis (SLE+P group; n = 46), SLE only (SLE group; n = 25), periodontitis only (P group; n = 58), and healthy individuals with no systemic or oral disease (H group; n = 44). Clinical periodontal condition was evaluated by measurement of probing depth, clinical attachment level, and alveolar bone loss. Genomic DNA was isolated from peripheral blood and analyzed for determination of FcgammaR genotypes (FcgammaRIIA, FcgammaRIIB, FcgammaRIIIA, and FcgammaRIIIB) and IL-1 genotypes (IL-1A +4845 and IL-1B +3954) by allele-specific polymerase chain reactions or DNA sequencing.


RESULTS
A significant overrepresentation of the R131 allele of stimulatory FcgammaRIIA and the 232T allele of inhibitory FcgammaRIIB was found in the SLE+P group compared to the H group (P = 0.01 and P = 0.0009, respectively). The combination of FcgammaRIIA-R131 and FcgammaRIIB-232T alleles yielded a strong association with SLE and periodontitis (SLE+P group versus P group: P = 0.01, odds ratio: 3.3; SLE+P group versus H group: P = 0.0009, odds ratio: 11.2). Furthermore, SLE patients with the combined FcgammaR risk alleles exhibited more severe periodontal tissue destruction compared to other SLE patients. The frequencies of IL-1 polymorphic alleles were too low to assess the association with SLE or periodontitis.


CONCLUSIONS
The combination of stimulatory FcgammaRIIA and inhibitory FcgammaRIIB genotypes may increase susceptibility to SLE and periodontitis in the Japanese population.
Kobayashi
Tetsuo
T
Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Ito
Satoshi
S
Yasuda
Keiko
K
Kuroda
Takeshi
T
Yamamoto
Kouji
K
Sugita
Noriko
N
Tai
Hideaki
H
Narita
Ichiei
I
Gejyo
Fumitake
F
Yoshie
Hiromasa
H
D000293:Adolescent; D000328:Adult; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics; D044466:Asian People; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D007564:Japan; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010518:Periodontitis / Q000150:complications* / Q000235:genetics* / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics*
D015703:Antigens, CD; C499173:FCGR2B protein, human; C080568:Fc gamma receptor IIA; D007141:Immunoglobulin Fc Fragments; D007375:Interleukin-1; D017452:Receptors, IgG