國家衛生研究院 NHRI:Item 3990099045/7175
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    题名: ALPK1 genetic regulation and risk in relation to gout
    作者: Ko, AMS;Tu, HP;Liu, TT;Chang, JG;Yuo, CY;Chiang, SL;Chang, SJ;Liu, YF;Ko, AMJ;Lee, CH;Lee, CP;Chang, CM;Tsai, SF;Ko, YC
    贡献者: Institute of Molecular and Genomic Medicine
    摘要: BACKGROUND: The present study investigated whether single nucleotide polymorphisms (SNPs) in the alpha-protein kinase 1 (ALPK1) gene are associated with gout in aboriginal and Han Chinese Taiwanese. METHODS: A total of 1351 aborigines from the community (511 cases and 840 controls) and 511 Han people from hospital (104 cases and 407 controls) were recruited. SNPs in potentially functional regions of the 38 genes within 4q25 were identified and genotypes determined by direct sequencing. Quantitation of blood ALPK1 mRNA expression levels and luciferase assay of gout-associated rs231253 pGL3-SNP constructs cotransfected with hsa-miR-519e were examined. RESULTS: We found that ALPK1 gene was the most determinant of gout. Three SNPs of rs11726117 M861T [C], rs231247 [G] and rs231253 [G] were most associated with gout risk [odd ratios (OR) >/=1.44, P </= 3.78 x 10-6) in aborigines. A replication set using Han people had risk at rs11726117 and rs231247 (OR >/=1.72, P </= 4.08 x 10-3). From pooled analysis (Breslow-Day test, P > 0.33) assuming an additive model, each increasing copy of the risk allele of rs11726117 [C], rs231247 [G] and rs231253 [G] showed significantly elevated OR for gout >/=1.42 (P >/= 1.53 x 10-6). Consistently, the composite homozygous of linked 3 SNPs (versus wild-type, OR = 1.83, P = 8.21 x 10-4) had strong associations with ALPK1 mRNA expression. Luciferase showed reduced hybridization between hsa-miR-519e and construct carrying gout-associated rs231253 [G] than the wild-type [C] (P = 6.19 x 10-4). CONCLUSIONS: Our study found that a newly identified ALPK1 gene can effectively interfere with microRNA target recognition and modulates the mRNA expression; and the varying distribution of the implicated SNPs among cases and controls in the two studied populations suggests a significant role in gout susceptibility.
    日期: 2013-04
    關聯: International Journal of Epidemiology. 2013 Apr;42(2):466-474.
    Link to: http://dx.doi.org/10.1093/ije/dyt028
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0300-5771&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000317627800021
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84877052602
    显示于类别:[張仲明] 期刊論文
    [蔡世峯] 期刊論文

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