Analysis of genetic variants of Alox12 (rs9904779) gene in periodontitis and type 2 diabetes mellitus

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-04-25 DOI:10.1016/j.genrep.2025.102236

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

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引用次数: 0

Abstract

Background

Periodontitis, a chronic inflammatory disease affecting tooth-supporting structures, shows increased tissue damage in type 2 diabetes patients, highlighting their bidirectional link. The Alox12 gene, encoding arachidonic acid 12-lipoxygenase, plays a role in inflammation and oxidation.

Objective

This study investigates Alox12 genetic variants in relation to periodontitis and T2DM.

Method

Genotyping of Alox12 rs9904779 in 400 individuals was conducted via PCR-RFLP. Statistical analysis was performed using Epi Info v.7.0, assessing genotype risk via odds ratio (OR) with 95 % CI and p < 0.05 as significant. HWE was evaluated, and genotype/allele frequencies were compared using the Chi-square test. RNA Fold evaluated mRNA structural impacts, while protein-protein docking and visualization were done using pyDOCKWEB.

Results

Statistically significant higher prevalence of the heterozygote CG genotype of rs9904779 showed a significant occurrence in the periodontitis patients (OR = 0.13, 95 % CI = 0.062-0.301, p = 0) and periodontitis with T2DM patients (OR = 0.08, 95 % CI = 0.036-0.188, p = 0) when compared to the healthy controls. The mRNA structure stability was found to be better with wild type (−950.68 kcal/mol) than variant (−950.61 kcal/mol). Alox12 was found to be interacting with gingipain and the bond length was found to be 12.731 A.

Conclusion

The study highlights a significant association between the Alox12 rs9904779 CG genotype and an increased risk of periodontitis and T2DM, suggesting its potential role in disease susceptibility. Additionally, structural and interaction analyses indicate that Alox12 may influence inflammatory pathways, providing insights into its functional impact.

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牙周炎和2型糖尿病患者Alox12 （rs9904779）基因变异分析

牙周炎是一种影响牙齿支撑结构的慢性炎症性疾病，在2型糖尿病患者中显示出更多的组织损伤，突出了它们之间的双向联系。Alox12基因编码花生四烯酸12-脂氧合酶，在炎症和氧化中起作用。目的探讨Alox12基因变异与牙周炎和2型糖尿病的关系。方法采用PCR-RFLP方法对400例患者的Alox12 rs9904779进行基因分型。使用Epi Info v.7.0进行统计分析，通过比值比（OR）评估基因型风险，95% CI和p <；0.05为显著性。评估HWE，并采用卡方检验比较基因型/等位基因频率。RNA Fold评估mRNA的结构影响，而蛋白对接和可视化使用pyDOCKWEB。结果rs9904779杂合子CG基因型在牙周炎患者（OR = 0.13, 95% CI = 0.062 ~ 0.301, p = 0）和T2DM牙周炎患者（OR = 0.08, 95% CI = 0.036 ~ 0.188, p = 0）中的患病率均高于健康对照组，差异有统计学意义。野生型（- 950.68 kcal/mol）的mRNA结构稳定性优于变异型（- 950.61 kcal/mol）。Alox12与gingipain相互作用，键长为12.731 A。结论：本研究强调Alox12 rs9904779 CG基因型与牙周炎和T2DM风险增加之间存在显著关联，提示其在疾病易感性中的潜在作用。此外，结构和相互作用分析表明，Alox12可能影响炎症途径，为其功能影响提供了见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.