https://scholars.lib.ntu.edu.tw/handle/123456789/632845
標題: | A Functional Polymorphism Downstream of Vitamin A Regulator Gene CYP26B1 Is Associated with Hand Osteoarthritis | 作者: | Khosasih, Vivia Liu, Kai-Ming Huang, Chung-Ming Liou, Lieh-Bang Hsieh, Ming-Shium Lee, Chian-Her Tsai, Chang-Youh Kuo, San-Yuan Hwa, Su-Yang CHIA-LI YU CHIH-HAO CHANG Lin, Cheng-Jyh SONG-CHOU HSIEH Cheng, Chun-Ying Chen, Wei-Ming Chen, Liang-Kuang Chuang, Hui-Ping Chen, Ying-Ting Tsai, Pei-Chun Lu, Liang-Suei H'ng, Weng-Siong Zhang, Yanfei Chen, Hsiang-Cheng Chen, Chien-Hsiun Lee, Ming Ta Michael Wu, Jer-Yuarn |
關鍵字: | CYP26B1; Han Chinese; genome-wide association study; hand osteoarthritis; polymorphisms; retinoic acid | 公開日期: | 3-二月-2023 | 出版社: | MDPI | 卷: | 24 | 期: | 3 | 來源出版物: | International journal of molecular sciences | 摘要: | While genetic analyses have revealed ~100 risk loci associated with osteoarthritis (OA), only eight have been linked to hand OA. Besides, these studies were performed in predominantly European and Caucasian ancestries. Here, we conducted a genome-wide association study in the Han Chinese population to identify genetic variations associated with the disease. We recruited a total of 1136 individuals (n = 420 hand OA-affected; n = 716 unaffected control subjects) of Han Chinese ancestry. We carried out genotyping using Axiom Asia Precisi on Medicine Research Array, and we employed the RegulomeDB database and RoadMap DNase I Hypersensitivity Sites annotations to further narrow down our potential candidate variants. Genetic variants identified were tested in the Geisinger's hand OA cohort selected from the Geisinger MyCode community health initiative (MyCode®). We also performed a luciferase reporter assay to confirm the potential impact of top candidate single-nucleotide polymorphisms (SNPs) on hand OA. We identified six associated SNPs (p-value = 6.76 × 10-7-7.31 × 10-6) clustered at 2p13.2 downstream of the CYP26B1 gene. The strongest association signal identified was rs883313 (p-value = 6.76 × 10-7, odds ratio (OR) = 1.76), followed by rs12713768 (p-value = 1.36 × 10-6, OR = 1.74), near or within the enhancer region closest to the CYP26B1 gene. Our findings showed that the major risk-conferring CC haplotype of SNPs rs12713768 and rs10208040 [strong linkage disequilibrium (LD); D' = 1, r2 = 0.651] drives 18.9% of enhancer expression activity. Our findings highlight that the SNP rs12713768 is associated with susceptibility to and severity of hand OA in the Han Chinese population and that the suggested retinoic acid signaling pathway may play an important role in its pathogenesis. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/632845 | ISSN: | 16616596 | DOI: | 10.3390/ijms24033021 |
顯示於: | 醫學系 |
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