title: Common variants of a urate-associated gene LRP2 are not associated with gout susceptibility.
abstract: A recent genome-wide association study revealed that there is an association between serum uric acid (SUA) levels and rs2544390, a common variant in low-density lipoprotein-related protein 2 (LRP2/Megalin) gene. Two other variants of LRP2, rs2229268 and rs3755166, are also found to have associations with dyslipidemia and Alzheimer's disease, respectively, which also could have a relationship with SUA in human. Although no studies report that LRP2 transports urate, LRP2 is a multi-ligand receptor and expresses in many tissues including kidney, suggesting a direct and/or indirect relationship with gout. In the present study, we investigated the association between gout and these variants of LRP2 with 741 clinically diagnosed male gout patients and 1,302 controls. As a result, the three common LRP2 variants, rs2544390, rs2229268 and rs3755166, showed no association with gout (P = 0.76, 0.55, and 0.22, respectively). Our study is the first to reveal that an SUA-related gene LRP2 is not involved in gout susceptibility.
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nakayama
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsuo
authors.forename: Toru
authors.initials: T
authors.lastname: Shimizu
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Takada
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Seiko
authors.initials: S
authors.lastname: Shimizu
authors.forename: Toshinori
authors.initials: T
authors.lastname: Chiba
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sakiyama
authors.forename: Mariko
authors.initials: M
authors.lastname: Naito
authors.forename: Emi
authors.initials: E
authors.lastname: Morita
authors.forename: Kimiyoshi
authors.initials: K
authors.lastname: Ichida
authors.forename: Nariyoshi
authors.initials: N
authors.lastname: Shinomiya
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006073:Gout / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007564:Japan; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D026561:Low Density Lipoprotein Receptor-Related Protein-2