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A common variant of LDL receptor related protein 2 (LRP2) gene is associated with gout susceptibility: a meta-analysis in a Japanese population.
Human Cell ( IF 4.3 ) Pub Date : 2020-01-24 , DOI: 10.1007/s13577-019-00318-5 Airi Akashi 1 , Akiyoshi Nakayama 1 , Yoichiro Kamatani 2, 3 , Toshihide Higashino 1 , Seiko Shimizu 1 , Yusuke Kawamura 1 , Misaki Imoto 1 , Mariko Naito 4, 5 , Asahi Hishida 4 , Makoto Kawaguchi 1 , Mikiya Takao 1 , Michinori Matsuo 6 , Tappei Takada 7 , Kimiyoshi Ichida 8 , Hiroshi Ooyama 9 , Nariyoshi Shinomiya 1 , Hirotaka Matsuo 1
Human Cell ( IF 4.3 ) Pub Date : 2020-01-24 , DOI: 10.1007/s13577-019-00318-5 Airi Akashi 1 , Akiyoshi Nakayama 1 , Yoichiro Kamatani 2, 3 , Toshihide Higashino 1 , Seiko Shimizu 1 , Yusuke Kawamura 1 , Misaki Imoto 1 , Mariko Naito 4, 5 , Asahi Hishida 4 , Makoto Kawaguchi 1 , Mikiya Takao 1 , Michinori Matsuo 6 , Tappei Takada 7 , Kimiyoshi Ichida 8 , Hiroshi Ooyama 9 , Nariyoshi Shinomiya 1 , Hirotaka Matsuo 1
Affiliation
Gout, which results from elevated serum uric acid (SUA), is a common form of arthritis that is induced by urate crystals. A single nucleotide polymorphism, rs2544390, of LDL receptor related protein 2 (LRP2/Megalin), has previously been reported to be associated with SUA by a genome-wide association study in a Japanese population. However, it was controversial as to whether rs2544390 is associated with gout in a Japanese population, since previous studies with Japanese populations have reported an association between gout and rs2544390 both with and without significance. This prompted us to investigate the association between gout and rs2544390 of LRP2. Using 1208 clinically diagnosed gout patients and 1223 controls in a Japanese male population, our results showed that while rs2544390 did not show a significant association with gout susceptibility in the present study (p = 0.0793, odds ratio [OR] with 95% confidential interval [CI] 1.11 [0.99–1.24]). However, a meta-analysis using previous studies on Japanese populations revealed a significant association with gout (pmeta = 0.0314, OR with 95% CI 1.09 [1.01–1.18]). We have therefore for the first time confirmed a positive association between rs2544390 and gout with only a Japanese male population. Our study provides clues to a better understanding of the pathogenesis of gout and has the potential to lead to novel therapeutic strategies against gout using LRP2 as a molecular target.
中文翻译：
低密度脂蛋白受体相关蛋白 2 (LRP2) 基因的常见变体与痛风易感性有关：日本人群的荟萃分析。
痛风是由血清尿酸 (SUA) 升高引起的，是一种常见的关节炎形式，由尿酸盐结晶诱发。先前在日本人群中进行的全基因组关联研究已报道LDL 受体相关蛋白 2 ( LRP2/Megalin ) 的单核苷酸多态性 rs2544390 与 SUA 相关。然而，关于 rs2544390 是否与日本人群中的痛风相关存在争议，因为之前对日本人群的研究报告了痛风与 rs2544390 之间的关联，无论是否具有显着性。这促使我们调查痛风与 LRP2 的rs2544390 之间的关联。在日本男性人群中使用 1208 名临床诊断的痛风患者和 1223 名对照，我们的结果表明，虽然 rs2544390 在本研究中与痛风易感性没有显着相关性（p = 0.0793，优势比 [OR] 和 95% 机密区间 [ CI] 1.11 [0.99–1.24]）。然而，使用先前对日本人群的研究进行的荟萃分析显示，痛风与痛风存在显着关联（p meta = 0.0314，或 95% CI 1.09 [1.01–1.18]）。因此，我们首次证实了 rs2544390 与痛风之间的正相关关系，仅与日本男性人群有关。我们的研究为更好地了解痛风的发病机制提供了线索，并有可能导致使用 LRP2 作为分子靶点来治疗痛风的新策略。
更新日期：2020-01-24
中文翻译：
低密度脂蛋白受体相关蛋白 2 (LRP2) 基因的常见变体与痛风易感性有关：日本人群的荟萃分析。
痛风是由血清尿酸 (SUA) 升高引起的，是一种常见的关节炎形式，由尿酸盐结晶诱发。先前在日本人群中进行的全基因组关联研究已报道LDL 受体相关蛋白 2 ( LRP2/Megalin ) 的单核苷酸多态性 rs2544390 与 SUA 相关。然而，关于 rs2544390 是否与日本人群中的痛风相关存在争议，因为之前对日本人群的研究报告了痛风与 rs2544390 之间的关联，无论是否具有显着性。这促使我们调查痛风与 LRP2 的rs2544390 之间的关联。在日本男性人群中使用 1208 名临床诊断的痛风患者和 1223 名对照，我们的结果表明，虽然 rs2544390 在本研究中与痛风易感性没有显着相关性（p = 0.0793，优势比 [OR] 和 95% 机密区间 [ CI] 1.11 [0.99–1.24]）。然而，使用先前对日本人群的研究进行的荟萃分析显示，痛风与痛风存在显着关联（p meta = 0.0314，或 95% CI 1.09 [1.01–1.18]）。因此，我们首次证实了 rs2544390 与痛风之间的正相关关系，仅与日本男性人群有关。我们的研究为更好地了解痛风的发病机制提供了线索，并有可能导致使用 LRP2 作为分子靶点来治疗痛风的新策略。
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