Genetic polymorphism of WNT9A is functionally associated with thumb osteoarthritis in the Chinese population.

IF 2 4区 医学 Q3 RHEUMATOLOGY Advances in Rheumatology Pub Date : 2024-01-29 DOI:10.1186/s42358-023-00337-9
Jian Dai, Haitao Jiang, Zhang Cheng, Yao Li, Zhaoqi Yang, Chuan Cheng, Xiaoming Tang
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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.

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中国人群中 WNT9A 基因多态性与拇指骨关节炎的功能相关。
背景:最近的一项全基因组关联研究发现,WNT9A的新型遗传变异与白种人拇指骨关节炎(TOA)的发病机制有关。我们的目的是在中国人群中复制WNT9A与TOA发病的关联,并进一步揭示风险变异的功能作用:方法:在953名TOA患者和1124名健康对照者中对WNT9A的SNP rs11588850进行基因分型。方法:对 953 名 TOA 患者和 1124 名健康对照者的 WNT9A SNP rs11588850 进行了基因分型,并使用 Chi-square 检验评估了患者和健康对照者之间基因型和等位基因分布的差异。用荧光素酶报告试剂盒检测变异对基因表达的影响:结果:TOA 患者基因型 AA 的频率明显低于对照组,分别为 74.9% 和 81.9%(Prs11588850的等位基因G可能通过上调WNT9A的表达与TOA风险增加有关。进一步对 rs11588850 在 WNT9A 表达中的调控作用进行功能分析,可为 TOA 的遗传结构提供新的线索。
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来源期刊
Advances in Rheumatology
Advances in Rheumatology Medicine-Rheumatology
CiteScore
4.00
自引率
4.30%
发文量
41
审稿时长
53 weeks
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.
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