Genetic association and epistatic interaction analysis of cluster of differentiation 14 and mannan-binding lectin 2 gene polymorphic variants in susceptibility to chronic periodontitis

Objective

To study the association and epistatic interactions of cluster of differentiation 14 (CD14) and mannan-binding lectin 2 (MBL2) gene polymorphic variants in Indian patients with chronic periodontitis (CP).

Design

We enrolled a total of 242 individuals (121 patients and 121 control subjects), age 35 to 60 years both irrespective of gender and identified CD14 (−159C > T, NC_000005.10:g.2569190:C > T) and MBL2 (codon 52, C > T, NM_000242:c.52C > T) polymorphic variants in peripheral blood samples. We also performed epistatic interaction analysis using multifactor dimensionality reduction (MDR) approach and predicted ribonucleic acid (RNA) structure of MBL2 gene using Genebee online RNA tool.

Results

Significantly increased frequency of ‘CT' heterozygote and variant allele ‘T' in chronic periodontitis patients was observed for both CD14 and MBL2 gene polymorphisms. MDR analysis showed approximately two-fold increased risk of CP. In silico analysis showed lack of transcription factor ETF (TEA domain family member 2) binding-site in presence of ‘T' allele ‘in CD14 (-159C > T) polymorphism. The secondary RNA structure prediction of MBL2 (codon 52, C > T) polymorphism showed structural variations having approximately similar free energies.

Conclusions

A dominant effect of genotype ‘CT' heterozygote and variant ‘T' allele observed for both CD14 and MBL2 gene polymorphisms in patients with CP. The presence of ‘T' allele also results in lack of transcription factor binding site at CD14 (-159C > T) and changes in arrangements of RNA molecules that may further affect expression of CD14 and MBL2 genes leading to increased susceptibility to CP pathogenesis.