24 November 2020

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A new genetic approach to identify those at high risk of generalized aggressive periodontitis

Lara Figini

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In this case-control study the authors selected some genes and loci which might be associated with generalized aggressive periodontitis  (GAgP), to identify the susceptibility genes of GAgP in the Chinese population.

Objective
Aggressive periodontitis (AgP) is a  rapid and severe progressive periodontitis. It occurs in the absence of systemic diseases and is characterized by familiarity. AgP can be  localized or generalized.

The generalized aggressive periodontitis (GAgP) is  characterized  by the loss of clinical attachment (AL) of at least three teeth, with the exception of the incisors and first molars, according to the 1999 International World Workshop classification of periodontal diseases and conditions. GAgP has a multifactorial etiology and a genetic predisposition. The genetic risk score (GRS) is an estimate of the cumulative contribution of genetic factors capable of developing susceptibility for certain diseases. This method has been widely used to investigate many diseases, including breast cancer, type 2 diabetes, schizophrenia, and other psychiatric disorders including Alzheimer's. Given the familiarity for GAgP, the GRS could therefore be useful for identifying subjects at high risk of GAgP.

Materials and methods
In a Chinese case-control study, published on Journal of Periodontology, July 2020 , the authors selected some genes and loci that could be associated with GAgP, to identify the GAgP susceptibility genes in the Chinese population. 335 patients with GAgP generalized aggressive periodontitis and 114 healthy controls were enrolled in the study. The inclusion criteria for patients with GAgP were as follows: patients <36 years with at least six teeth with PD pocket depth ≥ 5 mm, and clinical attachment loss AL ≥ 3 mm, with evident radiographic loss of interproximal bone, and familiar with generalized aggressive periodontitis verified by family history and periodontal examination of other family members. Whole blood samples were obtained from each test fasting and genomic DNA was extracted from each sample using a mini-kit according to the manufacturer's instructions. The GRS genetic risk score was calculated based on the achievement of significant levels of single nucleotide SNPs of the candidate gene (P <0.05). Four SNPs with susceptibility variants for GAgP were detected and therefore included in the calculation for the GRS. Two approaches were used to calculate the GRS: a simple risk allele counting method (unweighted GRS [uGRS]) and a weighted method (weighted GRS [wGRS]).Logistic regression models were performed for the association analyzes between GRS and GAgP risk.

Results
Four loci were significantly associated with GAgP and are:

- the matrix metalloproteinase 8 rs11225395

- the epidermal growth factor

- the PPARa rs4253623 e

- apolipoprotein E rs429358

Each additional point of uGRS / wGRS was associated with a 50% / 31% increased risk of developing GAgP after adjusting for age, gender, and body mass index (BMI). Participants assigned after genetic analysis to the uGRS / wGRS high-level group and the uGRS / wGRS medium-level group had an increased risk of GAgP compared to participants assigned to the uGRS / wGRS low-level group after adjustment for age, gender and BMI.

Conclusions
From the data of this study, which must be confirmed in other similar studies, it can be concluded that the GRS multi-locus genetic risk score based on four significant single nucleotide polymorphisms may be useful to assess the genetic predisposition to GAgP generalized aggressive periodontitis. .

Clinical implications
The GRS genetic risk score in combination with conventional risk factors can significantly improve the power of identification of individuals at high risk of GAgP.