Identification of rs671, a common variant of ALDH2, as a gout susceptibility locus.
Identification of rs671, a common variant of ALDH2, as a gout susceptibility locus.
复制标题
DOI：
10.1038/srep25360
复制
发表时间：
2016-05-16
影响因子：
4.6
通讯作者：
Shinomiya N
中科院分区：
文献类型：
--
作者：
Sakiyama M;Matsuo H;Nakaoka H;Yamamoto K;Nakayama A;Nakamura T;Kawai S;Okada R;Ooyama H;Shimizu T;Shinomiya N
痛风是一种常见的高尿酸血症引起的疾病。最近，一项全基因组关联研究确定了痛风与单核苷酸多态性（SNP）rs 2188380之间的关联，该SNP位于12号染色体上MYL 2和CUX 2之间的基因间区域。而rs 2188380附近的其他基因可能是痛风易感基因。因此，我们对MYL 2-CUX 2区域进行了精细定位研究。从MYL 2-CUX 2区域的8，595个SNP中选择9个标签SNP，并通过TaqMan方法对1，048名男性痛风患者和1，334名男性对照进行基因分型。Bonferroni校正后，8个SNP与痛风有显著相关性。ALDH 2的rs671（Glu 504 Lys）与痛风的相关性最显著（P = 1.7 × 10−18，比值比= 0.53）。在调整rs671后，其他8个SNP不再显示与痛风的显著关联，而rs671的显著关联仍然存在。据报道，rs671与饮酒行为有关，众所周知，饮酒会升高血清尿酸水平。这些数据表明，rs671，ALDH 2的一个常见的功能SNP，是MYL 2-CUX 2基因座中的一个真正的痛风相关SNP，并且rs671的“A”等位基因（Lys）在痛风的发展中起保护作用。
Gout is a common disease resulting from hyperuricemia. Recently, a genome-wide association study identified an association between gout and a single nucleotide polymorphism (SNP) rs2188380, located on an intergenic region between MYL2 and CUX2 on chromosome 12. However, other genes around rs2188380 could possibly be gout susceptibility genes. Therefore, we performed a fine-mapping study of the MYL2-CUX2 region. From 8,595 SNPs in the MYL2-CUX2 region, 9 tag SNPs were selected, and genotyping of 1,048 male gout patients and 1,334 male controls was performed by TaqMan method. Eight SNPs showed significant associations with gout after Bonferroni correction. rs671 (Glu504Lys) of ALDH2 had the most significant association with gout (P = 1.7 × 10−18, odds ratio = 0.53). After adjustment for rs671, the other 8 SNPs no longer showed a significant association with gout, while the significant association of rs671 remained. rs671 has been reportedly associated with alcohol drinking behavior, and it is well-known that alcohol drinking elevates serum uric acid levels. These data suggest that rs671, a common functional SNP of ALDH2, is a genuine gout-associated SNP in the MYL2-CUX2 locus and that “A” allele (Lys) of rs671 plays a protective role in the development of gout.