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

IF 1 Q4 GENETICS & HEREDITY Gene Reports Pub Date : 2025-02-11 DOI:10.1016/j.genrep.2025.102161

Usha Subbiah , Athira Ajith , Nihala Sidhic , Kaniha Sivakumar , Shaik Bibijanu , Hakeem Arishiya

{"title":"Human transferrin receptor gene polymorphism and its association with periodontitis and type 2 diabetes mellitus in south Indian population","authors":"Usha Subbiah , Athira Ajith , Nihala Sidhic , Kaniha Sivakumar , Shaik Bibijanu , Hakeem Arishiya","doi":"10.1016/j.genrep.2025.102161","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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 (<em>TFRC</em>) is a cell surface receptor required for iron uptake from a glycoprotein transferrin through receptor-mediated endocytosis. Host <em>genetic variants</em> play a major role in periodontal inflammation and T2DM, as they coexist as comorbidities.</div></div><div><h3>Aim</h3><div>To investigate the genetic association of <em>TFRC</em> upstream variant rs11915082 (G/A) and missense variant rs3817672 (C/T) in periodontitis and T2DM.</div></div><div><h3>Methods</h3><div>SNPs in the <em>TFRC</em> rs11915082 (G/A) and missense variant rs3817672 (C/T) were analysed by PCR RFLP. The study group included periodontitis (<em>n</em> = 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 <em>TFRC</em> wild type with rs11915082 and rs3817672 impact on mRNA's secondary structure, and its protein was docked with gingipain (Kgp) of <em>P. gingivalis</em> using in silico prediction analysis.</div></div><div><h3>Result</h3><div><em>TFRC</em> SNPs rs11915082 variant AA genotype was not significantly associated with risk of periodontitis and T2DM. However, rs3817672 heterozygous allele was a significant (<em>p</em>-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 (<em>TFRC</em>) with ASP 603.AN (Kgp) of <em>P. gingivalis</em>.</div></div><div><h3>Conclusion</h3><div>The <em>TFRC</em> missense variant rs3817672 could be used as a therapeutic marker for disease prognosis/diagnosis in periodontitis and T2DM.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"39 ","pages":"Article 102161"},"PeriodicalIF":1.0000,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gene Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2452014425000342","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

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.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

求助全文

约1分钟内获得全文去求助

来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.