Exploring the role of the WNT5A rs566926 polymorphism and its interactions in non-syndromic orofacial cleft: a multicenter study in Brazil.

IF 2.2 3区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Applied Oral Science Pub Date : 2024-02-12 eCollection Date: 2024-01-01 DOI:10.1590/1678-7757-2023-0353

Lorraynne Dos Santos Lara, Ricardo D Coletta, Renato Assis Machado, Lilianny Querino Rocha de Oliveira, Hercílio Martelli Júnior, Silvia Regina de Almeida Reis, Rafaela Scariot, Luiz Evaristo Ricci Volpato

{"title":"Exploring the role of the WNT5A rs566926 polymorphism and its interactions in non-syndromic orofacial cleft: a multicenter study in Brazil.","authors":"Lorraynne Dos Santos Lara, Ricardo D Coletta, Renato Assis Machado, Lilianny Querino Rocha de Oliveira, Hercílio Martelli Júnior, Silvia Regina de Almeida Reis, Rafaela Scariot, Luiz Evaristo Ricci Volpato","doi":"10.1590/1678-7757-2023-0353","DOIUrl":null,"url":null,"abstract":"Background: Associations between the WNT5A rs566926 variant and non-syndromic orofacial cleft (NSOC) have been reported in different populations.Objective: This study aimed to investigate the role of the rs566926 single nucleotide polymorphism (SNP) in WNT5A and its interactions with SNPs in BMP4, FGFR1, GREM1, MMP2, and WNT3 in the occurrence of NSOC in a Brazilian population.Methodology: A case-control genetic association study was carried out involving participants from four regions of Brazil, totaling 801 patients with non-syndromic cleft lip with or without cleft palate (NSCL±P), 273 patients with cleft palate only (NSCPO), and 881 health volunteers without any congenital condition (control). Applying TaqMan allelic discrimination assays, we evaluated WNT5A rs566926 in an ancestry-structured multiple logistic regression analysis, considering sex and genomic ancestry as covariates. Interactions between rs566926 and variants in genes involved in the WNT5A signaling pathway (BMP4, FGFR1, GREM1, MMP2, and WNT3) were also explored.Results: WNT5A rs566926 was significantly associated with an increased risk of NSCL±P, particularly due to a strong association with non-syndromic cleft lip only (NSCLO), in which the C allele increased the risk by 32% (OR: 1.32, 95% CI: 1.04-1.67, p=0.01). According to the proportions of European and African genomic ancestry, the association of rs566926 reached significant levels only in patients with European ancestry. Multiple interactions were detected between WNT5A rs566926 and BMP4 rs2071047, GREM1 rs16969681 and rs16969862, and FGFR1 rs7829058.Conclusion: The WNT5A rs566926 polymorphism was associated with NSCL±P, particularly in individuals with NSCLO and high European ancestry. Epistatic interactions involving WNT5A rs566926 and variants in BMP4, GREM1, and FGFR1 may contribute to the risk of NSCL±P in the Brazilian population.","PeriodicalId":15133,"journal":{"name":"Journal of Applied Oral Science","volume":"32 ","pages":"e20230353"},"PeriodicalIF":2.2000,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11018296/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Applied Oral Science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1590/1678-7757-2023-0353","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Associations between the WNT5A rs566926 variant and non-syndromic orofacial cleft (NSOC) have been reported in different populations.

Objective: This study aimed to investigate the role of the rs566926 single nucleotide polymorphism (SNP) in WNT5A and its interactions with SNPs in BMP4, FGFR1, GREM1, MMP2, and WNT3 in the occurrence of NSOC in a Brazilian population.

Methodology: A case-control genetic association study was carried out involving participants from four regions of Brazil, totaling 801 patients with non-syndromic cleft lip with or without cleft palate (NSCL±P), 273 patients with cleft palate only (NSCPO), and 881 health volunteers without any congenital condition (control). Applying TaqMan allelic discrimination assays, we evaluated WNT5A rs566926 in an ancestry-structured multiple logistic regression analysis, considering sex and genomic ancestry as covariates. Interactions between rs566926 and variants in genes involved in the WNT5A signaling pathway (BMP4, FGFR1, GREM1, MMP2, and WNT3) were also explored.

Results: WNT5A rs566926 was significantly associated with an increased risk of NSCL±P, particularly due to a strong association with non-syndromic cleft lip only (NSCLO), in which the C allele increased the risk by 32% (OR: 1.32, 95% CI: 1.04-1.67, p=0.01). According to the proportions of European and African genomic ancestry, the association of rs566926 reached significant levels only in patients with European ancestry. Multiple interactions were detected between WNT5A rs566926 and BMP4 rs2071047, GREM1 rs16969681 and rs16969862, and FGFR1 rs7829058.

Conclusion: The WNT5A rs566926 polymorphism was associated with NSCL±P, particularly in individuals with NSCLO and high European ancestry. Epistatic interactions involving WNT5A rs566926 and variants in BMP4, GREM1, and FGFR1 may contribute to the risk of NSCL±P in the Brazilian population.

查看原文本刊更多论文

探索 WNT5A rs566926 多态性及其相互作用在非综合征性口面裂中的作用：巴西的一项多中心研究。

背景：据报道，WNT5A rs566926 变体与非综合征性口唇裂（NSOC）之间存在关联：在不同人群中，WNT5A rs566926变异与非综合征性口唇裂（NSOC）之间的相关性已有报道：本研究旨在调查巴西人群中 WNT5A 的 rs566926 单核苷酸多态性（SNP）及其与 BMP4、FGFR1、GREM1、MMP2 和 WNT3 的 SNP 之间的相互作用在 NSOC 发生中的作用：这项病例对照遗传关联研究的参与者来自巴西四个地区，包括 801 名非综合征唇裂伴或不伴腭裂患者（NSCL±P）、273 名仅伴有腭裂的患者（NSCPO）和 881 名无任何先天性疾病的健康志愿者（对照组）。通过 TaqMan 等位基因鉴别分析，我们在祖先结构多元逻辑回归分析中评估了 WNT5A rs566926，并将性别和基因组祖先作为协变量。我们还探讨了 rs566926 与 WNT5A 信号通路相关基因（BMP4、FGFR1、GREM1、MMP2 和 WNT3）变异之间的相互作用：结果：WNT5A rs566926与NSCL±P风险增加显著相关，尤其是与非综合征性唇裂（NSCLO）密切相关，其中C等位基因增加了32%的风险（OR：1.32，95% CI：1.04-1.67，P=0.01）。根据欧洲和非洲基因组血统的比例，rs566926的相关性仅在欧洲血统的患者中达到显著水平。在 WNT5A rs566926 与 BMP4 rs2071047、GREM1 rs16969681 和 rs16969862 以及 FGFR1 rs7829058 之间检测到多种相互作用：WNT5A rs566926 多态性与 NSCL±P 相关，尤其是在 NSCLO 和高欧洲血统的个体中。WNT5A rs566926与BMP4、GREM1和FGFR1变异的外显相互作用可能会导致巴西人群罹患NSCL±P的风险。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Applied Oral Science 医学-牙科与口腔外科

CiteScore

4.80

自引率

3.70%

发文量

审稿时长

4-8 weeks

期刊介绍： The Journal of Applied Oral Science is committed in publishing the scientific and technologic advances achieved by the dental community, according to the quality indicators and peer reviewed material, with the objective of assuring its acceptability at the local, regional, national and international levels. The primary goal of The Journal of Applied Oral Science is to publish the outcomes of original investigations as well as invited case reports and invited reviews in the field of Dentistry and related areas.