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Go, Y.Y.,Kim, Y.S.,Cheon, S.,Nam, S.,Ku, K.B.,Kim, M.,Cho, N.H.,Park, H.,Alison Lee, P.Y.,Lin, Y.C.,Tsai, Y.L.,Thomas Wang, H.T.,Balasuriya, U.B.R. American Society for Investigative Pathology and t 2017 The Journal of Molecular Diagnostics Vol.19 No.6
<P>Middle East respiratory syndrome (MERS) is an emerging zoonotic viral respiratory disease that was first identified in Saudi Arabia in 2012. In 2015, the largest MERS outbreak outside of the Middle East region occurred in the Republic of Korea. The rapid nosocomial transmission of MERS-coronavirus (MERS-CoV) in Korean health care settings highlighted the importance and urgent need for a rapid and reliable on-site diagnostic assay to implement effective control and preventive measures. Here, the evaluation and validation of two newly developed reverse transcription insulated isothermal PCR (RT-iiPCR) methods targeting the ORF1a and upE genes of MERS-CoV are described. Compared with World Health Organization recommended singleplex real-time quantitative RT-PCR (RT-qPCR) assays, both RT-iiPCR assays had comparable analytical sensitivity for the detection of MERS-CoV RNA in tissue culture fluid and in sputum samples spiked with infectious virus. Furthermore, clinical evaluation was performed with sputum samples collected from subjects with acute and chronic respiratory illnesses, including patients infected with MERS-CoV. The overall agreement values between the two RT-iiPCR assays and the reference RT-qPCR assays were 98.06% (95% CI, 94.43%-100%; K = 0.96) and 99.03% (95% CI, 95.88%-100%; K = 0.99) for ORF1a and upE assays, respectively. The ORF1a and upE MERS-CoV RT-iiPCR assays coupled with a field deployable system provide a platform for a highly sensitive and specific on-site tool for diagnosis of MERS-CoV infections.</P>
Ma, R. C. W.,Hu, C.,Tam, C. H.,Zhang, R.,Kwan, P.,Leung, T. F.,Thomas, G. N.,Go, M. J.,Hara, K.,Sim, X.,Ho, J. S. K.,Wang, C.,Li, H.,Lu, L.,Wang, Y.,Li, J. W.,Wang, Y.,Lam, V. K. L.,Wang, J.,Yu, W.,Ki Springer-Verlag 2013 Diabetologia Vol.56 No.6
<P><B>Aims/hypothesis</B></P><P>Most genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians.</P><P><B>Methods</B></P><P>We performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations.</P><P><B>Results</B></P><P>We identified <I>CDKN2A/B</I> and four novel type 2 diabetes association signals with <I>p</I> < 1 × 10<SUP>−5</SUP> from the meta-analysis. Thirteen variants within these four loci were followed up in two independent Chinese cohorts, and rs10229583 at 7q32 was found to be associated with type 2 diabetes in a combined analysis of 11,067 cases and 7,929 controls (<I>p</I><SUB>meta</SUB> = 2.6 × 10<SUP>−8</SUP>; OR [95% CI] 1.18 [1.11, 1.25]). In silico replication revealed consistent associations across multiethnic groups, including five East Asian populations (<I>p</I><SUB>meta</SUB> = 2.3 × 10<SUP>−10</SUP>) and a population of European descent (<I>p</I> = 8.6 × 10<SUP>−3</SUP>). The rs10229583 risk variant was associated with elevated fasting plasma glucose, impaired beta cell function in controls, and an earlier age at diagnosis for the cases. The novel variant lies within an islet-selective cluster of open regulatory elements. There was significant heterogeneity of effect between Han Chinese and individuals of European descent, Malaysians and Indians.</P><P><B>Conclusions/interpretation</B></P><P>Our study identifies rs10229583 near <I>PAX4</I> as a novel locus for type 2 diabetes in Chinese and other populations and provides new insights into the pathogenesis of type 2 diabetes.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1007/s00125-013-2874-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users.</P>