A genome-wide association study reveals a quantitative trait locus of adiponectin on CDH13 that predicts cardiometabolic outcomes.
A genome-wide association study reveals a quantitative trait locus of adiponectin on CDH13 that predicts cardiometabolic outcomes.
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作者：
Chung CM;Lin TH;Chen JW;Leu HB;Yang HC;Ho HY;Ting CT;Sheu SH;Tsai WC;Chen JH;Lin SJ;Chen YT;Pan WH
血浆脂联素水平是代谢和心血管疾病的潜在上游和内部因素，具有相当高的遗传度。其他新基因是否影响脂联素水平的变化以及这些遗传变异对随后临床结果的作用尚未得到彻底研究。因此，我们的目的不仅是确定调节血浆脂联素水平的遗传变异，而且还调查这些变异是否与脂联素相关的代谢性状和心血管疾病。我们进行了一项全基因组关联研究（GWAS），以确定与高分子量形式的脂联素水平相关的数量性状位点（QTL），通过使用Illumina HumanHap 550 SNP芯片对382名高血压（YOH）受试者进行基因分型。然后在另外559名YOH受试者中证实了导致脂联素降低的罪魁祸首单核苷酸多态性（SNP）变异，并在一项独立的基于社区的前瞻性队列研究中检查了这些SNP变异与代谢综合征（MS）、2型糖尿病（T2 DM）和缺血性卒中风险的相关性，该前瞻性队列研究是血管疾病风险因素两乡镇研究（CVDFACTS，n = 3，350）。与脂联素水平最显著相关的SNP（rs 4783244）位于第一阶段T-cadherin（CDH 13）基因的内含子1（P = 7.57 × 10−9）。我们在另外559名YOH受试者中重复并证实了rs 4783244与血浆脂联素水平之间的相关性（P = 5.70 × 10−17）。在CVDFACTS中，该SNP进一步与MS（比值比[OR] = 1.42，P = 0.027）、男性T2 DM（OR = 3.25，P = 0.026）和缺血性卒中（OR = 2.13，P = 0.002）风险相关。这些发现表明T-钙粘蛋白在调节脂联素水平中的作用以及CDH 13或脂联素在心脏代谢疾病的发展中的参与。
The plasma adiponectin level, a potential upstream and internal facet of metabolic and cardiovascular diseases, has a reasonably high heritability. Whether other novel genes influence the variation in adiponectin level and the roles of these genetic variants on subsequent clinical outcomes has not been thoroughly investigated. Therefore, we aimed not only to identify genetic variants modulating plasma adiponectin levels but also to investigate whether these variants are associated with adiponectin-related metabolic traits and cardiovascular diseases. We conducted a genome-wide association study (GWAS) to identify quantitative trait loci (QTL) associated with high molecular weight forms of adiponectin levels by genotyping 382 young-onset hypertensive (YOH) subjects with Illumina HumanHap550 SNP chips. The culpable single nucleotide polymorphism (SNP) variants responsible for lowered adiponectin were then confirmed in another 559 YOH subjects, and the association of these SNP variants with the risk of metabolic syndrome (MS), type 2 diabetes mellitus (T2DM), and ischemic stroke was examined in an independent community–based prospective cohort, the CardioVascular Disease risk FACtors Two-township Study (CVDFACTS, n = 3,350). The SNP (rs4783244) most significantly associated with adiponectin levels was located in intron 1 of the T-cadherin (CDH13) gene in the first stage (P = 7.57 × 10−9). We replicated and confirmed the association between rs4783244 and plasma adiponectin levels in an additional 559 YOH subjects (P = 5.70 × 10−17). This SNP was further associated with the risk of MS (odds ratio [OR] = 1.42, P = 0.027), T2DM in men (OR = 3.25, P = 0.026), and ischemic stroke (OR = 2.13, P = 0.002) in the CVDFACTS. These findings indicated the role of T-cadherin in modulating adiponectin levels and the involvement of CDH13 or adiponectin in the development of cardiometabolic diseases.
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影响因子：
0.9
作者：
Liu, Pi-Hua;Jiang, Yi-Der;Chuang, Lee-Ming
通讯作者：
Chuang, Lee-Ming
影响因子：
5.3
作者：
Heid, Iris M.;Henneman, Peter;Hicks, Andrew;Coassin, Stefan;Winkler, Thomas;Aulchenko, Yurii S.;Fuchsberger, Christian;Song, Kijoung;Hivert, Marie-France;Waterworth, Dawn M.;Timpson, Nicholas J.;Richards, J. Brent;Perry, John R. B.;Tanaka, Toshiko;Amin, Najaf;Kollerits, Barbara;Pichler, Irene;Oostra, Ben A.;Thorand, Barbara;Frants, Rune R.;Illig, Thomas;Dupuis, Josee;Glaser, Beate;Spector, Tim;Guralnik, Jack;Egan, Josephine M.;Florez, Jose C.;Evans, David M.;Soranzo, Nicole;Bandinelli, Stefania;Carlson, Olga D.;Frayling, Timothy M.;Burling, Keith;Smith, George Davey;Mooser, Vincent;Ferrucci, Luigi;Meigs, James B.;Vollenweider, Peter;van Dijk, Ko Willems;Pramstaller, Peter;Kronenberg, Florian;van Duijn, Cornelia M.
通讯作者：
van Duijn, Cornelia M.
DOI：
10.1073/pnas.87.22.8751
发表时间：
1990-11-01
影响因子：
11.1
作者：
CARTER, BS;EWING, CM;ISAACS, WB
通讯作者：
ISAACS, WB
影响因子：
9.8
作者：
Jee, Sun Ha;Sull, Jae Woong;Beaty, Terri H.
通讯作者：
Beaty, Terri H.
影响因子：
6.9
作者：
Ling, Hua;Waterworth, Dawn M.;Stirnadel, Heide A.;Pollin, Toni I.;Barter, Philip J.;Kesaniemi, Y. Antero;Mahley, Robert W.;McPherson, Ruth;Waeber, Gerard;Bersot, Thomas P.;Cohen, Jonathan C.;Grundy, Scott M.;Mooser, Vincent E.;Mitchell, Braxton D.
通讯作者：
Mitchell, Braxton D.