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Kato, Norihiro,Takeuchi, Fumihiko,Tabara, Yasuharu,Kelly, Tanika N,Go, Min Jin,Sim, Xueling,Tay, Wan Ting,Chen, Chien-Hsiun,Zhang, Yi,Yamamoto, Ken,Katsuya, Tomohiro,Yokota, Mitsuhiro,Kim, Young Jin,O Nature Publishing Group, a division of Macmillan P 2011 Nature genetics Vol.43 No.6
We conducted a meta-analysis of genome-wide association studies of systolic (SBP) and diastolic (DBP) blood pressure in 19,608 subjects of east Asian ancestry from the AGEN-BP consortium followed up with de novo genotyping (n = 10,518) and further replication (n = 20,247) in east Asian samples. We identified genome-wide significant (P < 5 ? 10<SUP>??8</SUP>) associations with SBP or DBP, which included variants at four new loci (ST7L-CAPZA1, FIGN-GRB14, ENPEP and NPR3) and a newly discovered variant near TBX3. Among the five newly discovered variants, we obtained significant replication in the independent samples for all of these loci except NPR3. We also confirmed seven loci previously identified in populations of European descent. Moreover, at 12q24.13 near ALDH2, we observed strong association signals (P = 7.9 ? 10<SUP>??31</SUP> and P = 1.3 ? 10<SUP>??35</SUP> for SBP and DBP, respectively) with ethnic specificity. These findings provide new insights into blood pressure regulation and potential targets for intervention.
Kelly, Tanika N.,Takeuchi, Fumihiko,Tabara, Yasuharu,Edwards, Todd L.,Kim, Young Jin,Chen, Peng,Li, Huaixing,Wu, Ying,Yang, Chi-Fan,Zhang, Yonghong,Gu, Dongfeng,Katsuya, Tomohiro,Ohkubo, Takayoshi,Gao American Heart Association, Inc. 2013 Hypertension Vol.62 No.5
<P>We conducted a genome-wide association study meta-analysis of mean arterial pressure and pulse pressure among 26 600 East Asian participants (stage 1) followed by replication study of up to 28 783 participants (stage 2). For novel loci, statistical significance was determined by a <I>P</I><5.0×10<SUP>–8</SUP> in joint analysis of stage 1 and stage 2 data. For loci reported by the previous mean arterial and pulse pressure genome-wide association study meta-analysis in Europeans, evidence of transethnic replication was determined by consistency in effect direction and a Bonferroni-corrected <I>P</I><1.4×10<SUP>–3</SUP>. No novel loci were identified by the current study. Five independent mean arterial pressure variants demonstrated robust evidence for transethnic replication including rs17249754 at <I>ATP2B1</I> (<I>P</I>=7.5×10<SUP>–15</SUP>), rs2681492 at <I>ATP2B1</I> (<I>P</I>=3.4×10<SUP>–7</SUP>), rs11191593 at <I>NT5C2</I> (1.1×10<SUP>–6</SUP>), rs3824755 at <I>CYP17A1</I> (<I>P</I>=1.2×10<SUP>–6</SUP>), and rs13149993 at <I>FGF5</I> (<I>P</I>=2.4×10<SUP>–4</SUP>). Two additional variants showed suggestive evidence of transethnic replication (consistency in effect direction and <I>P</I><0.05), including rs319690 at <I>MAP4</I> (<I>P</I>=0.014) and rs1173771 at <I>NPR3</I> (<I>P</I>=0.018). For pulse pressure, robust evidence of replication was identified for 2 independent variants, including rs17249754 at <I>ATP2B1</I> (<I>P</I>=1.2×10<SUP>–5</SUP>) and rs11191593 at <I>NT5C2</I> (<I>P</I>=1.1×10<SUP>–3</SUP>), with suggestive evidence of replication among an additional 2 variants including rs3824755 at <I>CYP17A1</I> (<I>P</I>=6.1×10<SUP>–3</SUP>) and rs2681492 at <I>ATP2B1</I> (<I>P</I>=9.0×10<SUP>–3</SUP>). Replicated variants demonstrated consistency in effect sizes between East Asian and European samples, with effect size differences ranging from 0.03 to 0.24 mm Hg for mean arterial pressure and from 0.03 to 0.21 mm Hg for pulse pressure. In conclusion, we present the first evidence of transethnic replication of several mean arterial and pulse pressure loci in an East Asian population.</P>
Wen, Wanqing,Zheng, Wei,Okada, Yukinori,Takeuchi, Fumihiko,Tabara, Yasuharu,Hwang, Joo-Yeon,Dorajoo, Rajkumar,Li, Huaixing,Tsai, Fuu-Jen,Yang, Xiaobo,He, Jiang,Wu, Ying,He, Meian,Zhang, Yi,Liang, Jun IRL Press 2014 Human molecular genetics Vol.23 No.20
<P>Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by <I>in silico</I> and <I>de novo</I> replication among 7488–47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the <I>KCNQ1</I> (rs2237892, <I>P</I> = 9.29 × 10<SUP>−13</SUP>), <I>ALDH2/MYL2</I> (rs671, <I>P</I> = 3.40 × 10<SUP>−11</SUP>; rs12229654, <I>P</I> = 4.56 × 10<SUP>−9</SUP>), <I>ITIH4</I> (rs2535633, <I>P</I> = 1.77 × 10<SUP>−10</SUP>) and <I>NT5C2</I> (rs11191580, <I>P</I> = 3.83 × 10<SUP>−8</SUP>) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (<I>P</I> < 5.0 × 10<SUP>−8</SUP>) and an additional 14 at <I>P</I> < 1.0 × 10<SUP>−3</SUP> with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.</P>
Okada, Yukinori,Sim, Xueling,Go, Min Jin,Wu, Jer-Yuarn,Gu, Dongfeng,Takeuchi, Fumihiko,Takahashi, Atsushi,Maeda, Shiro,Tsunoda, Tatsuhiko,Chen, Peng,Lim, Su-Chi,Wong, Tien-Yin,Liu, Jianjun,Young, Terr Nature Publishing Group, a division of Macmillan P 2012 Nature genetics Vol.44 No.8
Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function??related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function??related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 ? 10<SUP>??8</SUP>). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ??10,347 individuals. We identify pleiotropic associations among these loci with kidney function??related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.
Genomic Basis for Methicillin Resistance in Staphylococcus aureus
Keiichi Hiramatsu,Teruyo Ito,Sae Tsubakishita,Takashi Sasaki,Fumihiko Takeuchi,Yuh Morimoto,Yuki Katayama,Miki Matsuo,Kyoko Kuwahara-Arai,Tomomi Hishinuma,Tadashi Baba 대한감염학회 2013 Infection and Chemotherapy Vol.45 No.2
Since the discovery of the first strain in 1961 in England, MRSA, the most notorious multidrug-resistant hospital pathogen, has spread all over the world. MRSA repeatedly turned down the challenges by number of chemotherapeutics, the fruits of modern organic chemistry. Now, we are in short of effective therapeutic agents against MRSA prevailing among immuno-compromised patients in the hospital. On top of this, we recently became aware of the rise of diverse clones of MRSA, some of which have increased pathogenic potential compared to the classical hospital-associated MRSA, and the others from veterinary sources. They increased rapidly in the community, and started menacing otherwise healthy individuals by causing unexpected acute infection. This review is intended to provide a whole picture of MRSA based on its genetic makeup as a versatile pathogen and our tenacious colonizer.
Nomura, Akihiro,Won, Hong-Hee,Khera, Amit V.,Takeuchi, Fumihiko,Ito, Kaoru,McCarthy, Shane,Emdin, Connor A.,Klarin, Derek,Natarajan, Pradeep,Zekavat, Seyedeh M.,Gupta, Namrata,Peloso, Gina M.,Borecki, Grune & Stratton 2017 Circulation research Vol.121 No.1
<P>Conclusions: Compared with noncarriers, carriers of PTV at CETP displayed higher high-density lipoprotein cholesterol, lower low-density lipoprotein cholesterol, lower triglycerides, and lower risk for CHD.</P>
Cho, Yoon Shin,Chen, Chien-Hsiun,Hu, Cheng,Long, Jirong,Hee Ong, Rick Twee,Sim, Xueling,Takeuchi, Fumihiko,Wu, Ying,Go, Min Jin,Yamauchi, Toshimasa,Chang, Yi-Cheng,Kwak, Soo Heon,Ma, Ronald C W,Yamamo Nature Publishing Group, a division of Macmillan P 2012 Nature genetics Vol.44 No.1
We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.