| 中文摘要 |
期刊連結：http://www.gouthyperuricemia.org
Objective: Gouty tophi are nodular mass deposits of monosodium urate (MSU) under the skin. Although environmental factors such as age and disease duration are considered as the major risks for gouty tophi, the genetic factors remain unclear. This study intended to explore the genetic risk components related to tophus occurrence using a genome-wide association study (GWAS).
Methods: Male gout patients were recruited with the tophus status recorded as a major outcome. Each tophaceous patient was matched to four non-tophus controls by their age and gouty disease duration. Affymetrix CHB SNP arrays were used to genotype the DNA samples and analyze associations with tophus occurrence.
Results: A total of 1888 male gout patients were included. Age and disease duration were the significant risk factors related to tophus occurrence. After matching by age and disease duration, 713 patients, composed of 145 gout patients with tophi and 568 without tophus, were included for further analysis. The GWAS results showed 12 SNPs that had significant associations with tophi occurrence (p<1×10-7), which were located in or near MSX2, CXCR5, PRKCE, MARCKS, PTPRD, DIRC3, TTLL7, KRT39, POLA2, PITX2, PITX1 and ADAM20 genes. By signaling pathway analysis, four SNPs near PKC-epsilon, MARCKS, PITX2, and MSX2 showed most significantly associations with each other, and were found to be associated with the process of tophi formation.
Conclusion: We concluded PKC-epsilon, MARCKS, Pitx2, and MSX2 were strongly associated with tophi occurrence via a potential role in the phagocytosis of MSU, NETosis, osteoblast retraction, and fibroblast formation of tophus, respectively. |
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