title: Common variant of ALPK1 is not associated with gout: a replication study.
abstract: Gout is one of the most kinds of common inflammatory arthritis as a consequence of hyperuricemia. Alpha-protein kinase 1 (ALPK1) gene locates in a gout-susceptibility locus on chromosome 4q21-31, and encodes ALPK1 protein which plays a pivotal role in the phosphorylation of myosin 1. In the previous genetic study of Taiwanese populations, 3 single nucleotide polymorphisms (SNPs), rs11726117, rs231247 and rs231253, in ALPK1 gene were reported to have a significant association with gout. However, no replication study has been performed to confirm this association. Therefore, we first conducted a replication study with clinically defined gout patients in a different population. Linkage disequilibrium (LD) analyzes of the 3 SNPs in ALPK1 revealed that these SNPs are in strong LD in a Japanese population. Among the 3 SNPs of ALPK1, rs11726117 (M861T) is the only missense SNP. Therefore, rs11726117 was genotyped in a Japanese population of 903 clinically defined gout cases and 1,302 controls, and was evaluated for a possible association with gout. The minor allele frequencies of rs11726117 were 0.26 and 0.25 in the case and control groups, respectively. The association analysis has not detected a significant association between rs11726117 and gout susceptibility in a Japanese population (p = 0.44). Because ABCG2, a major causative gene for gout, also locates in the gout-susceptibility locus on chromosome 4q, these findings suggest that among genes in a gout-susceptibility locus, not ALPK1 but ABCG2 could be important as a gout-susceptible gene.
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama, 359-8513, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Chiba
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsuo
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sakiyama
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nakayama
authors.forename: Seiko
authors.initials: S
authors.lastname: Shimizu
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakai
authors.forename: Shino
authors.initials: S
authors.lastname: Suma
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakashima
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Toru
authors.initials: T
authors.lastname: Shimizu
authors.forename: Kimiyoshi
authors.initials: K
authors.lastname: Ichida
authors.forename: Nariyoshi
authors.initials: N
authors.lastname: Shinomiya
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D044466:Asian People / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006073:Gout / Q000235:genetics*; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009218:Myosins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics; D010766:Phosphorylation; D020641:Polymorphism, Single Nucleotide; D011494:Protein Kinases / Q000235:genetics*; D015203:Reproducibility of Results; D013624:Taiwan
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D011494:Protein Kinases; D009218:Myosins