Common variant of BCAS3 is associated with gout risk in Japanese population: the first replication study after gout GWAS in Han Chinese.
Common variant of BCAS3 is associated with gout risk in Japanese population: the first replication study after gout GWAS in Han Chinese.
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DOI：
10.1186/s12881-018-0583-z
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发表时间：
2018-06-07
影响因子：
--
通讯作者：
Shinomiya N
中科院分区：
文献类型：
--
作者：
Sakiyama M;Matsuo H;Nakaoka H;Kawamura Y;Kawaguchi M;Higashino T;Nakayama A;Akashi A;Ueyama J;Kondo T;Wakai K;Sakurai Y;Yamamoto K;Ooyama H;Shinomiya N
痛风是由高尿酸血症引起的急性关节炎的常见疾病。最近的一项痛风全基因组关联研究（GWAS）在中国汉族人群中发现了三个新的痛风基因座：调节因子X3（RFX 3）、钾电压门控通道亚家族Q成员1（KCNQ 1）和乳腺癌扩增序列3（BCAS 3）。缺乏任何复制研究，这三个位点使用其他人群促使我们进行了复制研究与日本临床定义的痛风病例和对照。我们采用TaqMan方法对723例日本临床确诊的痛风患者和913例对照者进行RFX 3（rs 12236871）、KCNQ 1（rs 179785）和BCAS 3（rs 11653176）基因分型。KCNQ 1的rs 179785也通过直接测序进行评估，因为它的基因分型的TaqMan方法的困难。虽然RFX 3和BCAS 3的变异体可以通过TaqMan方法明确地进行基因分型，但KCNQ 1的rs 179785不能，因为KCNQ 1的rs 179785（A/G）位于KCNQ 1的12-bp缺失变异体（rs 200562977）的最后一个核苷酸（“A”）。因此，在所有样本中，通过直接测序对KCNQ 1的rs 179785和rs 200562977进行基因分型。此外，用相同的引物直接测序，我们能够评估KCNQ 1的rs 179784基因型，它与rs 179785显示出强连锁不平衡（D' = 1.0和r2 = 0.99）。rs 11653176是BCAS 3的一种常见变体，与痛风显著相关（P = 1.66 × 10− 3;比值比[OR] = 0.80）;作用方向与之前中国汉族GWAS中观察到的相同。KCNQ 1的两个变体（rs 179785和rs 179784）具有名义上的显著相关性（P = 0.043和0.044; OR = 0.85和0.86，分别），但未通过使用Bonferroni校正的多假设检验的显著性阈值。另一方面，KCNQ 1的rs 200562977和RFX 3的rs 12236871未显示与痛风有任何显著关联。BCAS 3是雌激素受体α的共激活剂，雌激素对血清尿酸水平的影响是众所周知的。我们目前的重复研究，如以前的痛风GWAS，证明了BCAS 3的常见变异与痛风易感性相关。
Gout is a common disease resulting from hyperuricemia which causes acute arthritis. A recent genome-wide association study (GWAS) of gout identified three new loci for gout in Han Chinese: regulatory factor X3 (RFX3), potassium voltage-gated channel subfamily Q member 1 (KCNQ1), and breast carcinoma amplified sequence 3 (BCAS3). The lack of any replication studies of these three loci using other population groups prompted us to perform a replication study with Japanese clinically defined gout cases and controls. We genotyped the variants of RFX3 (rs12236871), KCNQ1 (rs179785) and BCAS3 (rs11653176) in 723 Japanese clinically defined gout cases and 913 controls by TaqMan method. rs179785 of KCNQ1 is also evaluated by direct sequencing because of difficulties of its genotyping by TaqMan method. Although the variants of RFX3 and BCAS3 were clearly genotyped by TaqMan method, rs179785 of KCNQ1 was not, because rs179785 (A/G) of KCNQ1 is located at the last nucleotide (“A”) of the 12-bp deletion variant (rs200562977) of KCNQ1. Therefore, rs179785 and rs200562977 of KCNQ1 were genotyped by direct sequencing in all samples. Moreover, by direct sequencing with the same primers, we were able to evaluate the genotypes of rs179784 of KCNQ1 which shows strong linkage disequilibrium with rs179785 (D’ = 1.0 and r2 = 0.99). rs11653176, a common variant of BCAS3, showed a significant association with gout (P = 1.66 × 10− 3; odds ratio [OR] = 0.80); the direction of effect was the same as that seen in the previous Han Chinese GWAS. Two variants of KCNQ1 (rs179785 and rs179784) had a nominally significant association (P = 0.043 and 0.044; OR = 0.85 and 0.86, respectively), but did not pass the significance threshold for multiple hypothesis testing using the Bonferroni correction. On the other hand, rs200562977 of KCNQ1 and rs12236871 of RFX3 did not show any significant association with gout. BCAS3 is a coactivator of estrogen receptor alpha, and the influence of estrogen to serum uric acid level is well known. Our present replication study, as did the previous gout GWAS, demonstrated the common variant of BCAS3 to be associated with gout susceptibility.
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影响因子：
4.6
作者：
Matsuo H;Ichida K;Takada T;Nakayama A;Nakashima H;Nakamura T;Kawamura Y;Takada Y;Yamamoto K;Inoue H;Oikawa Y;Naito M;Hishida A;Wakai K;Okada C;Shimizu S;Sakiyama M;Chiba T;Ogata H;Niwa K;Hosoyamada M;Mori A;Hamajima N;Suzuki H;Kanai Y;Sakurai Y;Hosoya T;Shimizu T;Shinomiya N
通讯作者：
Shinomiya N
影响因子：
27.4
作者：
Nakayama A;Nakaoka H;Yamamoto K;Sakiyama M;Shaukat A;Toyoda Y;Okada Y;Kamatani Y;Nakamura T;Takada T;Inoue K;Yasujima T;Yuasa H;Shirahama Y;Nakashima H;Shimizu S;Higashino T;Kawamura Y;Ogata H;Kawaguchi M;Ohkawa Y;Danjoh I;Tokumasu A;Ooyama K;Ito T;Kondo T;Wakai K;Stiburkova B;Pavelka K;Stamp LK;Dalbeth N;Eurogout Consortium;Sakurai Y;Suzuki H;Hosoyamada M;Fujimori S;Yokoo T;Hosoya T;Inoue I;Takahashi A;Kubo M;Ooyama H;Shimizu T;Ichida K;Shinomiya N;Merriman TR;Matsuo H;Eurogout Consortium
通讯作者：
Eurogout Consortium
影响因子：
30.8
作者：
Sulem, Patrick;Gudbjartsson, Daniel F.;Stefansson, Kari
通讯作者：
Stefansson, Kari
影响因子：
27.4
作者：
Matsuo H;Yamamoto K;Nakaoka H;Nakayama A;Sakiyama M;Chiba T;Takahashi A;Nakamura T;Nakashima H;Takada Y;Danjoh I;Shimizu S;Abe J;Kawamura Y;Terashige S;Ogata H;Tatsukawa S;Yin G;Okada R;Morita E;Naito M;Tokumasu A;Onoue H;Iwaya K;Ito T;Takada T;Inoue K;Kato Y;Nakamura Y;Sakurai Y;Suzuki H;Kanai Y;Hosoya T;Hamajima N;Inoue I;Kubo M;Ichida K;Ooyama H;Shimizu T;Shinomiya N
通讯作者：
Shinomiya N
影响因子：
4.3
作者：
Sakiyama, Masayuki;Matsuo, Hirotaka;Shimizu, Seiko;Chiba, Toshinori;Nakayama, Akiyoshi;Takada, Yuzo;Nakamura, Takahiro;Takada, Tappei;Morita, Emi;Naito, Mariko;Wakai, Kenji;Inoue, Hiroki;Tatsukawa, Seishiro;Sato, Junki;Shimono, Kazumi;Makino, Toshiaki;Satoh, Takahiro;Suzuki, Hiroshi;Kanai, Yoshikatsu;Hamajima, Nobuyuki;Sakurai, Yutaka;Ichida, Kimiyoshi;Shimizu, Toru;Shinomiya, Nariyoshi
通讯作者：
Shinomiya, Nariyoshi