ALPK1 genetic regulation and risk in relation to gout.
- 作者：Ko AM(1), Tu HP, Liu TT, Chang JG, Yuo CY, Chiang SL, Chang SJ, Liu YF, Ko AM,Lee CH, Lee CP, Chang CM, Tsai SF, Ko YC. Int J Epidemiol. 2013 Apr;42(2):466-74. doi: 10.1093/ije/dyt028.
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.
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.
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 × 10(-6)) in aborigines. A replication set using Han people had risk at rs11726117 and rs231247 (OR ≥1.72, P ≤ 4.08 × 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 × 10(-6)). Consistently, the composite homozygous of linked 3 SNPs (versus wild-type, OR = 1.83, P = 8.21 × 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 × 10(-4)).
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.PMCID: PMC3695596
PMID: 23569188 [PubMed – indexed for MEDLINE]
Proinflammatory homeobox gene, ISX, regulates tumor growth and survival in
- 作者：Hsu SH(1), Wang LT, Lee KT, Chen YL, Liu KY, Suen JL, Chai CY, Wang SN. Cancer Res. 2013 Jan 15;73(2):508-18. doi: 10.1158/0008-5472.CAN-12-2795. Epub 2012 Dec 5.
- Chronic inflammation drives initiation of hepatocellular carcinoma (HCC), but the underlying mechanisms linking inflammation and tumor formation remain obscure. In this study, we compared the expression of interleukin (IL)-6 and cyclin D1 (CCND1) with the IL-6-induced homeobox gene ISX (intestine-specific homeobox) in 119 paired specimens of HCCs and adjacent normal tissues and also in paired specimens from 11 patients with non-HCCs. In pathologic analysis, ISX exhibited a tumor-specific expression pattern and a high correlation to patient survival time, tumor size, tumor number, and progression stage. Enforced expression of ISX accelerated cell proliferation and tumorigenic activity in hepatoma cells through CCND1 induction. In contrast, short hairpin RNA-mediated attenuation of ISX in hepatoma cells decreased cell proliferation and malignant transformation in vitro and in vivo. A high positive correlation existed in human hepatoma tumors between ISX and CCND1 expression. Together, our results highlight ISX as an important regulator in hepatoma progression with significant potential as a prognostic and therapeutic target in HCCs.
PMID: 23221382 [PubMed – indexed for MEDLINE]