Abstract
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.
Highlights
Gout is a common disease that results from an increase in serum uric acid (SUA), which can lead to renal failure, hypertension, and cardiovascular disease [1, 2]. rs2544390, a single nucleotide polymorphism (SNP) in LDL receptor
We investigated a further association between gout and rs2544390 with clinically diagnosed gout patients and controls, and performed a meta-analysis based on past Japanese population studies [4, 6]
We confirmed that rs2544390, an SNP of LDL receptor related protein 2 (LRP2), has an association with gout in the Japanese population
Summary
Gout is a common disease that results from an increase in serum uric acid (SUA), which can lead to renal failure, hypertension, and cardiovascular disease [1, 2]. rs2544390, a single nucleotide polymorphism (SNP) in LDL receptor1 3 Vol.:(0123456789)related protein 2 (LRP2, known as Megalin), was found to have an association with SUA in a genome-wide association study (GWAS) with 8868 Japanese [3]. Gout is a common disease that results from an increase in serum uric acid (SUA), which can lead to renal failure, hypertension, and cardiovascular disease [1, 2]. Rs2544390, a single nucleotide polymorphism (SNP) in LDL receptor. Related protein 2 (LRP2, known as Megalin), was found to have an association with SUA in a genome-wide association study (GWAS) with 8868 Japanese [3]. The association between rs2544390 and gout remained to be clarified, because some studies, including ours, have reported no association [4, 5], while others have revealed a significant association [5–7]. We investigated a further association between gout and rs2544390 with clinically diagnosed gout patients and controls, and performed a meta-analysis based on past Japanese population studies [4, 6]
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