{"title":"Genetic polymorphism of WNT9A is functionally associated with thumb osteoarthritis in the Chinese population.","authors":"Jian Dai, Haitao Jiang, Zhang Cheng, Yao Li, Zhaoqi Yang, Chuan Cheng, Xiaoming Tang","doi":"10.1186/s42358-023-00337-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>In a recent genome-wide association study, novel genetic variations of WNT9A were reported to be involved in the etiopathogenesis of thumb osteoarthritis (TOA) in Caucasians. Our purposes were to replicate the association of WNT9A with the development of TOA in the Chinese population and to further unveil the functional role of the risk variants.</p><p><strong>Methods: </strong>SNP rs11588850 of WNT9A were genotyped in 953 TOA patients and 1124 healthy controls. The differences of genotype and allele distributions between the patients and healthy controls were evaluated using the Chi-square test. Luciferase Reporter Assay was performed to investigate the influence of variant on the gene expression.</p><p><strong>Results: </strong>There was significantly lower frequency of genotype AA in TOA patients than in the controls 74.9% vs. 81.9%, p < 0.001). The frequency of allele A was remarkably lower in the patients than in the controls (86.3% vs. 90.5%, p < 0.001), with an odds ratio of 0.66 (95% CI = 0.54-0.80). Luciferase Reporter Assay showed that the construct containing mutant allele G of rs11588850 displayed 29.1% higher enhancer activity than the wild allele A construct (p < 0.05).</p><p><strong>Conclusions: </strong>Allele G of rs11588850 was associated with the increased risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA.</p>","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":null,"pages":null},"PeriodicalIF":2.0000,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in Rheumatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s42358-023-00337-9","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: In a recent genome-wide association study, novel genetic variations of WNT9A were reported to be involved in the etiopathogenesis of thumb osteoarthritis (TOA) in Caucasians. Our purposes were to replicate the association of WNT9A with the development of TOA in the Chinese population and to further unveil the functional role of the risk variants.
Methods: SNP rs11588850 of WNT9A were genotyped in 953 TOA patients and 1124 healthy controls. The differences of genotype and allele distributions between the patients and healthy controls were evaluated using the Chi-square test. Luciferase Reporter Assay was performed to investigate the influence of variant on the gene expression.
Results: There was significantly lower frequency of genotype AA in TOA patients than in the controls 74.9% vs. 81.9%, p < 0.001). The frequency of allele A was remarkably lower in the patients than in the controls (86.3% vs. 90.5%, p < 0.001), with an odds ratio of 0.66 (95% CI = 0.54-0.80). Luciferase Reporter Assay showed that the construct containing mutant allele G of rs11588850 displayed 29.1% higher enhancer activity than the wild allele A construct (p < 0.05).
Conclusions: Allele G of rs11588850 was associated with the increased risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA.
期刊介绍:
Formerly named Revista Brasileira de Reumatologia, the journal is celebrating its 60th year of publication.
Advances in Rheumatology is an international, open access journal publishing pre-clinical, translational and clinical studies on all aspects of paediatric and adult rheumatic diseases, including degenerative, inflammatory and autoimmune conditions. The journal is the official publication of the Brazilian Society of Rheumatology and welcomes original research (including systematic reviews and meta-analyses), literature reviews, guidelines and letters arising from published material.