Keenan, Tanya and Zhao, Wei and Rasheed, Asif and Ho, Weang K. and Malik, Rainer and Felix, Janine F. and Young, Robin and Shah, Nabi and Samuel, Maria and Sheikh, Nasir and Mucksavage, Megan L. and Shah, Omar and Li, Jin and Morley, Michael and Laser, Annika and Mallick, Nadeem Hayat and Zaman, Khan Shah and Ishaq, Mohammad and Rasheed, Syed Zahed and Memon, Fazal-ur-Rehman and Ahmed, Faisal and Hanif, Bashir and Lakhani, Muhammad Shakir and Fahim, Muhammad and Ishaq, Madiha and Shardha, Naresh Kumar and Ahmed, Naveeduddin and Mahmood, Khalid and Iqbal, Waseem and Akhtar, Saba and Raheel, Rabia and O'Donnell, Christopher J. and Hengstenberg, Christian and Maerz, Winifred and Kathiresan, Sekar and Samani, Nilesh and Goel, Anuj and Hopewell, Jemma C. and Chambers, John and Cheng, Yu-Ching and Sharma, Pankaj and Yang, Qiong and Rosand, Jonathan and Boncoraglio, Giorgio B. and Kazmi, Shahana Urooj and Hakonarson, Hakon and Koettgen, Anna and Kalogeropoulos, Andreas and Frossard, Philippe and Kamal, Ayeesha and Dichgans, Martin and Cappola, Thomas and Reilly, Muredach P. and Danesh, John and Rader, Daniel J. and Voight, Benjamin F. and Saleheen, Danish (2016) Causal Assessment of Serum Urate Levels in Cardiometabolic Diseases Through a Mendelian Randomization Study. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 67 (4). pp. 407-416. ISSN 0735-1097, 1558-3597
Full text not available from this repository. (Request a copy)Abstract
BACKGROUND Although epidemiological studies have reported positive associations between circulating urate levels and cardiometabolic diseases, causality remains uncertain. OBJECTIVES Through a Mendelian randomization approach, we assessed whether serum urate levels are causally relevant in type 2 diabetes mellitus (T2DM), coronary heart disease (CHD), ischemic stroke, and heart failure (HF). METHODS This study investigated 28 single nucleotide polymorphisms known to regulate serum urate levels in association with various vascular and nonvascular risk factors to assess pleiotropy. To limit genetic confounding, 14 single nucleotide polymorphisms exclusively associated with serum urate levels were used in a genetic risk score to assess associations with the following cardiometabolic diseases (cases/controls): T2DM (26,488/83,964), CHD (54,501/68,275), ischemic stroke (14,779/67,312), and HF (4,526/18,400). As a positive control, this study also investigated our genetic instrument in 3,151 gout cases and 68,350 controls. RESULTS Serum urate levels, increased by 1 SD due to the genetic score, were not associated with T2DM, CHD, ischemic stroke, or HF. These results were in contrast with previous prospective studies that did observe increased risks of these 4 cardiometabolic diseases for an equivalent increase in circulating urate levels. However, a 1 SD increase in serum urate levels due to the genetic score was associated with increased risk of gout (odds ratio: 5.84; 95% confidence interval: 4.56 to 7.49), which was directionally consistent with previous observations. CONCLUSIONS Evidence from this study does not support a causal role of circulating serum urate levels in T2DM, CHD, ischemic stroke, or HF. Decreasing serum urate levels may not translate into risk reductions for cardiometabolic conditions. (C) 2016 by the American College of Cardiology Foundation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; URIC-ACID; BLOOD-PRESSURE; GENETIC-VARIANTS; COMMON VARIANTS; ISCHEMIC-STROKE; ARTERY-DISEASE; INCREASED RISK; LOCI; genetic; pleiotropy; single nucleotide polymorphism |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Mar 2019 12:31 |
| Last Modified: | 12 Mar 2019 12:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2419 |
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