17 November 2022

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

Simona Chirico

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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.  

Generalized aggressive periodontitis (GAgP) is characterized by the loss of clinical attachment (AL) of at least three teeth, except for 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 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 elevated risk of GAgP.  

Materials and methods  

In a study conducted by Li et al., the authors selected genes and loci that could be associated with GAgP, to identify the GAgP susceptibility genes in the Chinese population.  

Researchers enrolled 335 patients with GAgP generalized aggressive periodontitis and 114 healthy controls. The inclusion criteria for patients with GAgP were as follows:  

• Patients less than 36 years old 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. Patients also had generalized aggressive periodontitis verified by family history and family members also received a periodontal examination.  

Whole blood samples were obtained, 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: - matrix metalloproteinase 8 rs11225395 - epidermal growth factor - 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

The multi-locus GRS based on four significant single nucleotide polymorphisms might be useful to assess genetic predisposition to GAgP. The GRS in combination with conventional risk factors significantly improved the power of identifying subgroups of Chinese population with a particularly high risk for GAgP.

Wenjing Li, Xian'e Wang, Yu Tian, ​​Li Xu, Li Zhang, Dong Shi, Xianghui Feng, Ruifang Lu, Huanxin Meng. “A novel multi-locus genetic risk score identifies patients with higher risk of generalized aggressive periodontitis.” J Periodontol. 2020 Jul; 91 (7): 925-932. https://doi.org/10.1002/JPER.19-0135