Association of Increased Levels of Fibrinogen and the –455G/A Fibrinogen Gene Polymorphism with Chronic Periodontitis

Abstract

Fibrinogen is one of the acute-phase proteins whose levels are elevated during periodontal disease. Recent studies suggest that excessive fibrinogen production might play a role in upregulating host immune responses. In addition, there is a relationship between the -455G/A polymorphism (HaeIII) in the 5' flanking region of the beta-fibrinogen gene promoter and increased fibrinogen levels. In this study, we investigated the distribution of the -455G/A polymorphism and the relationship of this specific genotype to fibrinogen levels in periodontitis patients. In order to assess the -455G/A polymorphism, restriction fragment length polymorphism (RFLP) analysis with HaeIII enzyme was performed in the promoter region of the beta-fibrinogen gene. This was carried out on 79 chronic periodontitis patients as compared to 75 periodontally healthy subjects, matched to age, gender, and race. Fibrinogen levels were determined by the radial immunodiffusion assay (RID). The frequency of homozygocity for the rare allele of the beta-fibrinogen gene (H2H2) was 13% for the periodontitis patients and 3% for the control group (P = 0.01). The distributions of H1H1 and H1H2 genotypes were 48% and 39% in the patient group and 70% and 27% in the control group, respectively. Chi-square analysis indicated that the distribution of these genotypes between the 2 groups was significantly different (P = 0.01). Fibrinogen levels were significantly higher in the patient group (2,496.5 mg/l +/- 105) compared to the control group (2,250.0 mg/l +/- 118.3) after adjusting for age, gender, and smoking status (P = 0.04). Consistent with previous reports, in our study population, those subjects with the H2H2 genotype had significantly higher fibrinogen levels (3,005.7 mg/l +/- 182.5) compared to subjects with the H1H1 genotype (2,325.0 mg/l +/- 91.6) or H1H2 genotype (2,438.0 mg/l +/- 117.4) (P = 0.001). Furthermore, the H1H2 and H2H2 genotypes were found at a higher frequency among periodontitis patients than controls. The odds ratios (OR) for these genotypes were 3.26 (95% confidence interval [CI]: 1.25 to 8.53) for the H1H2 genotype and 6.41 (95% CI: 1.15 to 35.83) for the H2H2 genotype as compared to individuals with the H1H1 genotype, after adjusting for age, gender, and smoking status. The results indicate that a higher percentage of chronic periodontitis patients exhibit genotypes associated with higher plasma fibrinogen levels than healthy individuals. Furthermore, periodontitis patients have significantly higher fibrinogen levels compared to healthy individuals. The presence of H1H2 or H2H2 genotypes as well as elevated fibrinogen levels, in conjunction with other factors, may put individuals at higher risk of having periodontal disease, or may result from periodontal infection-genetic interactions.