Epistasis Between Two Gene Variants of Leptin and Vascular Endothelial Growth Factor Genes in the Development of Primary Knee Osteoarthritis.

IF 1.4 4区医学 Q2 Medicine

Revista De Investigacion Clinica-Clinical and Translational Investigation Pub Date : 2022-03-15 DOI:10.24875/RIC.21000493

Matvey Sosa-Arellano, Norma C González-Huerta, Eugenio Morales-Hernández, Carolina Duarte-Salazar, Antonio Miranda-Duarte

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引用次数: 2

Abstract

Background: The association of leptin (LEP) and vascular endothelial growth factor A (VEGFA) genes with the susceptibility to knee osteoarthritis (OA) has been analyzed; however, the epistasis between them has not been investigated.

Objective: The objective of the study was to analyze the association of LEP and VEGFA variants and their interaction with primary knee OA in a Mexican Mestizo population.

Methods: A case-control study was developed. Cases were ≥40 years, BMI ≤27 kg/m², with primary knee OA and radiologic Grade ≥2. Controls were participants with no knee OA and a radiologic Grade < 2. The rs2167270 of LEP and rs2010963 of VEGFA were genotyped. Genotypic association was tested under codominant, dominant, and recessive models. Uni- and multi-variate analyses were developed through non-conditional logistic regression. The multifactor dimensionality reduction algorithm was developed to detect epistasis.

Results: Participants comprised 103 cases and 179 controls. Allelic and genotypic distributions did not show differences between the groups. Notwithstanding, a statistically significant interaction was observed between the LEP and VEGFA genes (p = 0.02) with a testing accuracy of 0.5199 and cross-validation consistency of 10/10. This interaction model confers an increased risk to knee OA (OR [95% CI] = 1.8 [1.1-2.9]).

Conclusion: Interaction between LEP and VEGFA is related with genetic susceptibility to developing primary knee OA.

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瘦素和血管内皮生长因子基因两种基因变异在原发性膝关节骨关节炎发病中的作用。

背景:本文分析了瘦素(LEP)和血管内皮生长因子A (VEGFA)基因与膝骨关节炎(OA)易感性的关系;然而，它们之间的上位性尚未得到研究。目的:本研究的目的是分析墨西哥Mestizo人群中LEP和VEGFA变异的相关性及其与原发性膝关节OA的相互作用。方法:采用病例对照研究。患者年龄≥40岁，BMI≤27 kg/m2，伴有原发性膝关节OA，影像学分级≥2级。对照组为无膝关节炎且放射学分级< 2的参与者。对LEP基因rs2167270和VEGFA基因rs2010963进行基因分型。基因型关联在共显性、显性和隐性模型下进行检验。通过非条件逻辑回归进行单变量和多变量分析。开发了多因素降维算法来检测上位性。结果:参与者包括103例病例和179例对照。等位基因和基因型分布在组间无差异。尽管如此，LEP和VEGFA基因之间存在统计学显著的相互作用(p = 0.02)，检测精度为0.5199，交叉验证一致性为10/10。这种相互作用模型增加了膝关节OA的风险(OR [95% CI] = 1.8[1.1-2.9])。结论:LEP和VEGFA的相互作用与原发性膝关节OA的遗传易感性有关。

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

Revista De Investigacion Clinica-Clinical and Translational Investigation 医学-医学：内科

CiteScore

3.00

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： The Revista de Investigación Clínica – Clinical and Translational Investigation (RIC-C&TI), publishes original clinical and biomedical research of interest to physicians in internal medicine, surgery, and any of their specialties. The Revista de Investigación Clínica – Clinical and Translational Investigation is the official journal of the National Institutes of Health of Mexico, which comprises a group of Institutes and High Specialty Hospitals belonging to the Ministery of Health. The journal is published both on-line and in printed version, appears bimonthly and publishes peer-reviewed original research articles as well as brief and in-depth reviews. All articles published are open access and can be immediately and permanently free for everyone to read and download. The journal accepts clinical and molecular research articles, short reports and reviews. Types of manuscripts: – Brief Communications – Research Letters – Original Articles – Brief Reviews – In-depth Reviews – Perspectives – Letters to the Editor