國家衛生研究院 NHRI:Item 3990099045/7620
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    題名: Common quantitative trait locus downstream of RETN gene identified by genome-wide association study is associated with risk of type 2 diabetes mellitus in Han Chinese: A Mendelian randomization effect
    作者: Chung, CM;Lin, TH;Chen, JW;Leu, HB;Yin, WH;Ho, HY;Sheu, SH;Tsai, WC;Chen, JH;Lin, SJ;Pan, WH
    貢獻者: Division of Health Services and Preventive Medicine
    摘要: OBJECTIVE: Plasma resistin level is a potential molecular link between obesity and diabetes. Causal role of resistin, type 2 diabetes mellitus (T2DM) and genetic variants have not been thoroughly investigated Therefore, we conducted a genome-wide association study (GWAS) to identify quantitative trait loci associated with resistin levels and investigated whether these variants were prospectively associated with the development of metabolic syndrome (MetS) and T2DM in an independent community-based cohort, the CardioVascular Disease risk FACtors Two-township Study (CVDFACTS). RESEARCH DESIGN AND METHODS: We genotyped 382 young-onset hypertensive (YOH) subjects with Illumina HumanHap550 SNP chips and searched for QTLs of resistin in the 1st stage GWAS and confirmed the finding in another 559 YOH subjects. Logistic regression was used to examine the Mendelian randomization effects between genotypes of confirmed QTLs and metabolic outcomes in 3400 subjects of CVDFACTS. RESULTS: Two SNPs (rs3745367 and rs1423096) were significantly associated with resistin levels (p = 5.52x10-15 and p = 2.54 x 10-20 ) and replicated in another 559 YOH subjects (p = 1.29x10-3 and p = 1.13 x 10-7 ), respectively. The SNP rs1423096 was further associated with the levels of HDL-C (p = 0.006), the risk of MetS (OR = 2.21, p = 0.0034), and T2DM (OR = 1.62, p = 0.0063) in the CVDFACTS. People with the haplotypes A-G and G-G determined by rs3745367 and rs1423096 showed a significantly increased T2DM risk (p = 0.0068 and p = 0.0035 respectively) compared with those with A-A haplotype. CONCLUSION: We have found that rs3745367 and rs1423096 on the RETN gene were significantly associated with resistin levels. However, rs1423096, downstream of RETN, seems to be associated with MetS and T2DM risk more so than rs3745367. The established genotype-disease association points to a causal association resistin and T2DM.
    日期: 2014-03
    關聯: Diabetes-Metabolism Research and Reviews. 2014 Mar;30(3):232-240.
    Link to: http://dx.doi.org/10.1002/dmrr.2481
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1520-7552&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000333022600007
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84895492184
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