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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/5833


    Title: Replication of genome-wide association signals of type 2 diabetes in han Chinese in a prospective cohort
    Authors: Chang, YC;Chiu, YF;Liu, PH;Shih, KC;Lin, MW;Sheu, WH;Quertermous, T;Curb, JD;Hsiung, CA;Lee, WJ;Lee, PC;Chen, YT;Chuang, LM
    Contributors: Division of Biostatistics and Bioinformatics
    Abstract: Bcakground: A recent genome-wide association study for type 2 diabetes in Han Chinese identified several novel genetic variants. We investigated their associations with quantitative measures to explore the mechanism by which these variants influence glucose homeostasis. We also examined whether these variants predict progression to diabetes in a large prospective family-based Chinese cohort. Methods: Five single nucleotide polymorphisms (SNPs) near the PTPRD, SRR, MAF/WWOX, and KCNQ1 genes were genotyped in 1,138 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) study. Results: At baseline, the risk-conferring rs7192960 C allele near the MAF/WWOX genes was associated with lower homeostasis model assessment of beta-cell (HOMA-beta)(P=0.01) and second-phase insulin response in oral glucose tolerance test (OGTT) (P=0.04). The risk-conferring rs2237897 C alleles in the KCNQ1 gene were associated with higher fasting glucose (P=0.009), lower HOMA-beta(P=0.03), and lower first-phase insulin response in OGTT (P=0.03). Over an average follow-up period of 5.43 years, participants with the risk-conferring rs17584499 TT genotype in the PTPRD gene were more likely to progress from non-diabetes to diabetes than were non-carriers (hazard ratio: 8.82, P=4x10(-5) ). The risk-conferring T allele in the PTPRD gene was associated with greater increase in homeostasis model assessment of insulin resistance (HOMA-IR) (P=0.04) over time. PTPRD gene expression in human adipose tissues was negatively associated with fasting insulin levels and HOMA-IR. Conclusion: Genetic variants near the KCNQ1 and MAF/WWOX genes are associated with reduced insulin secretion. The PTPRD genetic variant appears to be associated with progression to diabetes in Han Chinese, most likely through increased insulin resistance.
    Date: 2012-03
    Relation: Clinical Endocrinology. 2012 Mar;76(3):365-372.
    Link to: http://dx.doi.org/10.1111/j.1365-2265.2011.04175.x
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0300-0664&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000299946000009
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84863046601
    Appears in Collections:[熊昭] 期刊論文
    [邱燕楓] 期刊論文

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