南印度人群转铁蛋白受体基因多态性及其与牙周炎和2型糖尿病的关系

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

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引用次数: 0

摘要

牙周炎是一种牙龈疾病，它会破坏支撑牙齿的软组织和骨骼。2型糖尿病（T2DM）是一种以胰岛素生成受损为特征的代谢性疾病。牙周炎通过增加炎症状态加重糖尿病。转铁蛋白受体（TFRC）是通过受体介导的内吞作用从糖蛋白转铁蛋白中摄取铁所需的细胞表面受体。宿主遗传变异在牙周炎症和2型糖尿病中起主要作用，因为它们作为合并症共存。目的探讨TFRC上游变异rs11915082 （G/A）和错义变异rs3817672 （C/T）在牙周炎和T2DM中的遗传关系。方法采用PCR RFLP分析TFRC rs11915082 （G/A）和错义变体rs3817672 （C/T）的snp。研究组包括牙周炎（n = 100）、T2DM （n = 100）、牙周炎合并T2DM （n = 100）和健康对照组（n = 100）。共病变异的遗传关联通过测序得到证实。进一步研究rs11915082和rs3817672对TFRC野生型mRNA二级结构的影响，并将其蛋白与牙龈卟啉（P. gingivalis）的gingipain （Kgp）对接，应用计算机预测分析。结果frc snp rs11915082变异AA基因型与牙周炎和T2DM风险无显著相关。而rs3817672杂合等位基因显著(p值<；0.05)携带者患病风险与变异等位基因T显著相关(优势比>；1（95%可信区间），有牙周炎、2型糖尿病和合并症的风险。因此，rs3817672 SNP的杂合子CT和纯合子变异TT基因型显示为牙周炎和T2DM的危险SNP。野生型比rs3817672的稳定性好，变异rs11915082的稳定性好。分子相互作用残基为SER598。AC （TFRC）与ASP 603。牙龈假单胞菌的AN （Kgp）。结论TFRC错义变异体rs3817672可作为牙周炎和T2DM患者疾病预后/诊断的治疗性标志物。

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

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.

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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.