使用Next Generation Sequence及SnapShot assay確認ABCG2及SLC22A12與國人痛風的相關性

The SNPs of ABCG2, not SLC22A12, is Associated with Gout by Next Generation Sequence and Snapshot Assay Validation Among Taiwanese Population

台灣目前痛風盛行率為全世界第一，且有逐漸年輕化的趨勢。已有研究指出在調節血液中尿酸濃度的SLC22A12及ABCG2上發現的SNPs與痛風都具有相關性，但在國內的相關資料還需釐清。利用次世代定序來分析正常、高尿酸血症及痛風族群各48、19及48支檢體。結果顯示ABCG2上的兩個hotspots，分別為rs2231142及rs4148155，在正常及痛風族群有顯著的差異（p value ＜0.05，oddsratio及95%CI均為3.98及2.16~7.32），再用Snapshot assay分析後與NGS結果比對，專一性為100%。未來可基於本研究成果進而建立檢測套組來供國人檢測。

Gout is characterized by hyperuriceamia, which is super-saturation of uric acid in the blood. Underexcretion of uric acid, which is the most important in the hyperuriceamia. SLC22A12 and ABCG2 are two major regulators of the uric acid homeostasis. According to previous findings, some sensitive single nucleotide polymorphisms (SNPs) in the SLC22A12 and ABCG2 genes are correlated with the hyperuriceamia and gout in the different populations. However, the genetic study of SLC22A12 and ABCG2 is still unclear in Taiwanese population. Therefore, the aims of this study is to explore the unique sensitive SNPs in the SLC22A12 and ABCG2 genes, which are correlated with hyperuriceamia or gout among Taiwanese population and use the sensitive and low-cost approach, such as SnapShot assay, to detect the sensitive SNPs rapidly for clinical application. In this study, we use the NGS approach to detect normal, hyperuricemia and gout populations. The results of this study indicate the twelve hotspots of SLC22A12 in normal and hyperuricemia or gout population did not show significant differences. On the other hand, rs2231142 and rs4148155 of ABCG2 have significant differences in normal and gout groups (p value ＜0.05, odds ratio and 95%CI are both 3.98 and 2.16~7.32). The specificity of the comparison result in the Snapshot assay and NGS panel is 100%. In conclusion, the clinical application of the present study could be established in the future.