Copy Number Variants of the DEFA1A3 gene and chronic periodontitis

We have previously shown that salivary concentrations of alpha-defensins (HNP1-3) may be a useful biomarker of periodontal disease.  The DEFA1A3 gene codes for HNP 1- 3 and occurs in multiple copy numbers typically between 3 and 12, with a reported median number of 6 copies.  Copy number variants (CNV) have been associated with total concentrations of HNP 1- 3 production in different subjects.  Therefore the aim of this pilot study was to investigate the hypothesis that CNVs of the DEFA1A3 gene may be associated with risk of chronic periodontitis (CP).

Methods:

Following informed consent, genomic DNA was extracted from whole blood of 161 patients with moderate – severe chronic periodontitis attending the Periodontal Clinic, Guys Dental Hospital.   Samples were analysed by qPCR using a custom made CNV Assay (Applied Biosystems).  Analysis using the CopyCaller® software generated the CNV scores for all the samples.  CNV numbers were compared with previously published data of DEFA1A3 CNVs in a UK population as a reference population of unknown periodontal status.

Results:

DNA from patients with CP showed a range of CNVs of the DEFA1A3 gene between 6 – 13, with a median number of 6.  Data were dichotomized into subjects with CNV of ≤ 6, and those with > 6 copies.  60.2 % of CP samples had CNV of ≤ 6;  however in the published reference population the proportion of subjects with ≤ 6 copies was only 45%.  These differences were significantly different by Fisher’s Exact test ( P = 0.02)

Conclusions:

These pilot data suggest the possibility that CNV of the DEFA1A3 gene may be a significant susceptibility factor for periodontal disease.  Further, larger studies with additional reference populations are required to confirm this finding.