Detection of susceptibility loci on APOA5 and COLEC12 associated with metabolic syndrome using a genome-wide association study in a Taiwanese population
ONCOTARGET
Authors: Lin, Eugene; Kuo, Po-Hsiu; Liu, Yu-Li; Yang, Albert C.; Tsai, Shih-Jen
Abstract
Background: Although the association of single nucleotide polymorphisms (SNPs) with metabolic syndrome (MetS) has been reported in various populations in several genome-wide association studies (GWAS), the data is not conclusive. In this GWAS study, we assessed whether SNPs are associated with MetS and its individual components independently and/or through complex interactions in a Taiwanese population. Methods: A total of 10,300 Taiwanese subjects were assessed in this study. Metabolic traits such as waist circumference, triglyceride, high-density lipoprotein (HDL) cholesterol, systolic and diastolic blood pressure, and fasting glucose were measured. Results: Our data showed an association of MetS at the genome-wide significance level (P < 8.6 x 10(-8)) with two SNPs, including the rs662799 SNP in the apolipoprotein A5 (APOA5) gene and the rs16944558 SNP in the collectin subfamily member 12 (COLEC12) gene. Moreover, we identified the effect of APOA5 rs662799 on triglyceride and HDL, the effect of rs1106475 in the actin filament associated protein 1 like 2 (AFAP1L2) gene on systolic blood pressure, and the effect of rs17667932 in the mediator complex subunit 30 (MED30) gene on fasting glucose. Additionally, we found that an interaction between the APOA5 rs662799 and COLEC12 rs16944558 SNPs influenced MetS, high triglyceride, and low HDL. Conclusions: Our study indicates that the APOA5 and COLEC12 genes may contribute to the risk of MetS and its individual components independently as well as through gene-gene interactions.
The knockdown of the mediator complex subunit MED30 suppresses the proliferation and migration of renal cell carcinoma cells
ANNALS OF DIAGNOSTIC PATHOLOGY
Authors: Syring, Isabella; Weiten, Richard; Mueller, Tim; Schmidt, Doris; Steiner, Susanne; Mueller, Stefan C.; Kristiansen, Glen; Ellinger, Joerg
Abstract
Background: The mediator complex consists of 33 subunits and plays a central role in transcription. Studies have already described the involvement of individual subunits, especially in carcinogenesis. With regard to the subunit MED30, this has, so far, only been confirmed in gastric and breast carcinoma. The role of MED30 in urological tumours is unknown. Materials and methods: First, a database analysis using cBioPortal was performed for the mRNA expression and survival analysis of MED30 in clear cell renal cell carcinoma (ccRCC) and papillary RCC (pRCC). The immunohistochemical analysis (IHC) against MED30 was performed on tissue microarrays (TMA), with benign, ccRCC, pRCC samples, and ccRCC-metastases. Intensity evaluation was performed using the IRS (Immunoreactive Score). The ccRCC cell lines ACHN and A-498 were used for the functional investigation of proliferation, migration, and invasion after the knockdown of MED30 by siRNA. Results: In a database analysis by cBioPortal, it was shown that mRNA overexpression of MED30 in the pRCC was significantly associated with a poorer overall survival and progression-free survival. In the IHC, pRCC showed the highest level of MED30 expression, unfortunately without significant results in the survival analysis. The knockdown of MED30 resulted in a significant decrease in proliferation, migration, and invasion in ccRCC. Conclusion: In summary, MED30 seems to be involved in the progression of the RCC.