Chiba Toshinori, Matsuo Hirotaka, Sakiyama Masayuki, Nakayama Akiyoshi, Shimizu Seiko, Wakai Kenji, Suma Shino, Nakashima Hiroshi, Sakurai Yutaka, Shimizu Toru, Ichida Kimiyoshi, Shinomiya Nariyoshi
Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama, 359-8513, Japan.
Hum Cell. 2015 Jan;28(1):1-4. doi: 10.1007/s13577-014-0103-1. Epub 2014 Oct 19.
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.
痛风是高尿酸血症导致的最常见的炎性关节炎之一。α-蛋白激酶1（ALPK1）基因位于4号染色体q21 - 31的痛风易感位点，编码在肌球蛋白1磷酸化过程中起关键作用的ALPK1蛋白。在之前对台湾人群的基因研究中，据报道ALPK1基因中的3个单核苷酸多态性（SNP），即rs11726117、rs231247和rs231253，与痛风存在显著关联。然而，尚未进行重复研究来证实这种关联。因此，我们首先在不同人群中对临床确诊的痛风患者进行了重复研究。对ALPK1基因中这3个SNP的连锁不平衡（LD）分析表明，这些SNP在日本人群中处于强连锁不平衡状态。在ALPK1的3个SNP中，rs11726117（M861T）是唯一的错义SNP。因此，在903例临床确诊的痛风病例和1302例对照的日本人群中对rs11726117进行基因分型，并评估其与痛风的可能关联。rs11726117在病例组和对照组中的次要等位基因频率分别为0.26和0.25。关联分析未在日本人群中检测到rs11726117与痛风易感性之间存在显著关联（p = 0.44）。由于痛风的主要致病基因ABCG2也位于4号染色体q的痛风易感位点，这些发现表明，在痛风易感位点的基因中，作为痛风易感基因，重要的可能不是ALPK1而是ABCG2。
