FAM5C Contributes to Aggressive Periodontitis

Abstract

Aggressive periodontitis is characterized by a rapid and severe periodontal destruction in young systemically healthy subjects. A greater prevalence is reported in Africans and African descendent groups than in Caucasians and Hispanics. We first fine mapped the interval 1q24.2 to 1q31.3 suggested as containing an aggressive periodontitis locus. Three hundred and eighty-nine subjects from 55 pedigrees were studied. Saliva samples were collected from all subjects, and DNA was extracted. Twenty-one single nucleotide polymorphisms were selected and analyzed by standard polymerase chain reaction using TaqMan chemistry. Non-parametric linkage and transmission distortion analyses were performed. Although linkage results were negative, statistically significant association between two markers, rs1935881 and rs1342913, in the FAM5C gene and aggressive periodontitis (p = 0.03) was found. Haplotype analysis showed an association between aggressive periodontitis and the haplotype A-G (rs1935881-rs1342913; p = 0.009). Sequence analysis of FAM5C coding regions did not disclose any mutations, but two variants in conserved intronic regions of FAM5C, rs57694932 and rs10494634, were found. However, these two variants are not associated with aggressive periodontitis. Secondly, we investigated the pattern of FAM5C expression in aggressive periodontitis lesions and its possible correlations with inflammatory/immunological factors and pathogens commonly associated with periodontal diseases. FAM5C mRNA expression was significantly higher in diseased versus healthy sites, and was found to be correlated to the IL-1β, IL-17A, IL-4 and RANKL mRNA levels. No correlations were found between FAM5C levels and the presence and load of red complex periodontopathogens or Aggregatibacter actinomycetemcomitans. This study provides evidence that FAM5C contributes to aggressive periodontitis.

TBX21-1993T/C (rs4794067) polymorphism is associated with increased risk of chronic periodontitis and increased T-bet expression in periodontal lesions, but does not significantly impact the IFN-g transcriptional level or the pattern of periodontophatic bacterial infection

“…DNA integrity was checked and the allelic discrimination of TBX21-1993T/C SNP (rs4794067) variants was performed in 3 mL reactions using Taqman (Applied Biosystems, Warrington, UK) chemistry as previously described. 48,49 Genotyping was performed blinded to group status. For reaction quality control, a sample of known genotype was included in the plate and a no DNA template sample was included as negative control.…”

Mucosal Transcriptomics Implicates Under Expression of BRINP3 in the Pathogenesis of Ulcerative Colitis

“…The BRINP3 gene has been correlated with myocardial infarction 60 and aggressive periodonitis 61 in genetic studies. It has been postulated that it could play a role in osteoblast differentation.…”

Family with Sequence Similarity 5, Member C (FAM5C) Increases Leukocyte Adhesion Molecules in Vascular Endothelial Cells: Implication in Vascular Inflammation

“…The results of most studies implicate FAM5C as a disease marker, although the association between FAM5C and periodontitis is controversial [8], [18]. However, the contribution of FAM5C to the phenotype of each disease remains largely unknown.…”

“…An association between the expression of FAM5C and tongue squamous cell carcinoma [5], the hypermethylation of the FAM5C gene in gastric cancer [7], and a genetic association between polymorphisms within the FAM5C gene and aggressive periodontitis [8] have been reported. A genome-wide association study identified a genetic association between polymorphisms within the FAM5C gene and myocardial infarction, thereby implicating FAM5C as a risk factor for myocardial infarction [9].…”