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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/6343


    Title: Genetic variation in the carbonyl reductase 3 gene confers risk of type 2 diabetes and insulin resistance: a potential regulator of adipogenesis
    Authors: Chang, YC;Liu, PH;Tsai, YC;Chiu, YF;Shih, SR;Ho, LT;Lee, WJ;Lu, CH;Quertermous, T;Curb, JD;Lee, PC;He, YH;Yeh, JI;Hwang, JJ;Tsai, SH;Chuang, LM
    Contributors: Division of Biostatistics and Bioinformatics
    Abstract: Prostaglandins are potent modulators of insulinsensitivity. We systemically evaluated the association of 61tag single-nucleotide polymorphisms (SNP) in 14 genesinvolved in prostaglandin metabolism with type 2 diabetes.Among all genotyped SNPs, rs10483032 in the CBR3(carbonyl reductase 3) gene, which encodes for an enzymeconverting prostaglandin E 2 to prostaglandin F2α, was as-sociated with type 2 diabetes in 760 type 2 diabetic casesand 760 controls (stage-1 study) ( P0 2.0×10− 4). The asso-ciation was validated in 1,615 cases and 1,162 controls(stage-2 study) ( P0 0.009). The A allele at rs10483032 wasassociated with increased risk of type 2 diabetes (oddsratio 0 1.29; 95% confidence interval 0 1.14 – 1.47; combinedP <0.0001). The association was externally validated in theFinland – United States Investigation of NIDDM Genetics(FUSION) study ( P0 3.7×10− 4). The risk A allele was as-sociated with higher homeostasis model assessment of in-sulin resistance (HOMA-IR) in 1,012 non-diabetic controlsand 1,138 non-diabetic subjects from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance(SAPPHIRe) family study. CBR3 gene expression in humanabdominal adipose tissue was negatively associated withfasting insulin and HOMA-IR. CBR3 gene expression in-creased during differentiation of 3T3-L1 preadipocytes intoadipocytes. Knockdown of CBR3 in 3T3-L1 preadipocytesenhanced adipogenesis and peroxisome proliferator – activa-tor receptor –γ response element reporter activity. Ourresults indicated that genetic polymorphism in the CBR3gene conferred risk of type 2 diabetes and insulin resistancein Chinese. The association was probably mediated throughmodulation of adipogenesis.
    Date: 2012-07
    Relation: Journal of Molecular Medicine. 2012 Jul;90(7):847-858.
    Link to: http://dx.doi.org/10.1007/s00109-012-0898-8
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0946-2716&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000305734700013
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84865147062
    Appears in Collections:[邱燕楓] 期刊論文

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