Human transferrin receptor gene polymorphism and its association with periodontitis and type 2 diabetes mellitus in south Indian population

Abstract

Background

Periodontitis, the gum disease breakdown the soft tissue and bone that supports the teeth. Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterised by impaired insulin production. Periodontitis aggravates diabetes by increasing the inflammatory status. Transferrin receptor (TFRC) is a cell surface receptor required for iron uptake from a glycoprotein transferrin through receptor-mediated endocytosis. Host genetic variants play a major role in periodontal inflammation and T2DM, as they coexist as comorbidities.

Aim

To investigate the genetic association of TFRC upstream variant rs11915082 (G/A) and missense variant rs3817672 (C/T) in periodontitis and T2DM.

Methods

SNPs in the TFRC rs11915082 (G/A) and missense variant rs3817672 (C/T) were analysed by PCR RFLP. The study group included periodontitis (n = 100), T2DM (n = 100), periodontitis with T2DM (n = 100), and healthy control (n = 100). The genetic association of the variants of the comorbidity was confirmed by sequencing. Further TFRC wild type with rs11915082 and rs3817672 impact on mRNA's secondary structure, and its protein was docked with gingipain (Kgp) of P. gingivalis using in silico prediction analysis.

Result

TFRC SNPs rs11915082 variant AA genotype was not significantly associated with risk of periodontitis and T2DM. However, rs3817672 heterozygous allele was a significant (p-value < 0.05) carrier for disease risk and the variant allele T was significantly associated (odds ratio > 1 with 95 % confidence interval) with the risk for periodontitis, T2DM and in comorbid subjects. Hence the heterozygous CT and homozygous variant TT genotypes of rs3817672 SNP exhibited as a risk SNP for both periodontitis and T2DM. The wild-type had better stability than rs3817672 and vice versa in the variant rs11915082. The molecular interacting residues were SER598.AC (TFRC) with ASP 603.AN (Kgp) of P. gingivalis.

Conclusion

The TFRC missense variant rs3817672 could be used as a therapeutic marker for disease prognosis/diagnosis in periodontitis and T2DM.