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A causal relationship between uric acid and diabetic macrovascular disease in Chinese type 2 diabetes patients: A Mendelian randomization analysis

Abstract Background As the association between uric acid and macrovascular disease has been heavily debated, we aimed to confirm whether there is a causal relationship between uric acid and diabetic macrovascular disease through Mendelian randomization analysis. Methods In 3207 type 2 diabetes patie...

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Published in:International journal of cardiology 2016-07, Vol.214, p.194-199
Main Authors: Yan, Dandan, Wang, Jie, Jiang, Feng, Zhang, Rong, Wang, Tao, Wang, Shiyun, Peng, Danfeng, He, Zhen, Chen, Haibing, Bao, Yuqian, Hu, Cheng, Jia, Weiping
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container_title International journal of cardiology
container_volume 214
creator Yan, Dandan
Wang, Jie
Jiang, Feng
Zhang, Rong
Wang, Tao
Wang, Shiyun
Peng, Danfeng
He, Zhen
Chen, Haibing
Bao, Yuqian
Hu, Cheng
Jia, Weiping
description Abstract Background As the association between uric acid and macrovascular disease has been heavily debated, we aimed to confirm whether there is a causal relationship between uric acid and diabetic macrovascular disease through Mendelian randomization analysis. Methods In 3207 type 2 diabetes patients, seventeen SNPs (single nucleotide polymorphisms) related to uric acid were genotyped. A weighted GRS (genetic risk score) was calculated using selected SNPs and the strength of their effects on uric acid levels. Diabetic macrovascular disease was diagnosed through vascular ultrasound, magnetic resonance imaging or other clinical evidence. Associations of diabetic macrovascular disease with uric acid and weighted GRS were evaluated separately. Results In total participants and among females, the prevalence of diabetic macrovascular disease was significantly higher in hyperuricemic group than in normouricemic group, and uric acid was associated with diabetic macrovascular disease (OR = 1.068, p = 0.0349; OR = 1.122, p = 0.0158). The prevalence of diabetic macrovascular disease increased with the weighted GRS in a J-shaped manner for the females. The weighted GRS was positively correlated with uric acid in total population, male patients and female patients (β = 0.203, p < 0.0001; β = 0.255, p < 0.0001; β = 0.142, p < 0.0001, respectively). The weighted GRS was significantly associated with diabetic macrovascular disease in female patients (OR = 1.184, p = 0.0039). Among females, the observed association between weighted GRS and diabetic macrovascular disease was greater than predicted. Conclusions Using the uric acid-related weighted GRS as an instrumental variable for Mendelian randomization analysis, our study provided an evidence for causal relationship between uric acid and diabetic macrovascular disease in Chinese females with type 2 diabetes mellitus.
doi_str_mv 10.1016/j.ijcard.2016.03.206
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Methods In 3207 type 2 diabetes patients, seventeen SNPs (single nucleotide polymorphisms) related to uric acid were genotyped. A weighted GRS (genetic risk score) was calculated using selected SNPs and the strength of their effects on uric acid levels. Diabetic macrovascular disease was diagnosed through vascular ultrasound, magnetic resonance imaging or other clinical evidence. Associations of diabetic macrovascular disease with uric acid and weighted GRS were evaluated separately. Results In total participants and among females, the prevalence of diabetic macrovascular disease was significantly higher in hyperuricemic group than in normouricemic group, and uric acid was associated with diabetic macrovascular disease (OR = 1.068, p = 0.0349; OR = 1.122, p = 0.0158). The prevalence of diabetic macrovascular disease increased with the weighted GRS in a J-shaped manner for the females. The weighted GRS was positively correlated with uric acid in total population, male patients and female patients (β = 0.203, p &lt; 0.0001; β = 0.255, p &lt; 0.0001; β = 0.142, p &lt; 0.0001, respectively). The weighted GRS was significantly associated with diabetic macrovascular disease in female patients (OR = 1.184, p = 0.0039). Among females, the observed association between weighted GRS and diabetic macrovascular disease was greater than predicted. Conclusions Using the uric acid-related weighted GRS as an instrumental variable for Mendelian randomization analysis, our study provided an evidence for causal relationship between uric acid and diabetic macrovascular disease in Chinese females with type 2 diabetes mellitus.</description><identifier>ISSN: 0167-5273</identifier><identifier>EISSN: 1874-1754</identifier><identifier>DOI: 10.1016/j.ijcard.2016.03.206</identifier><identifier>PMID: 27064641</identifier><language>eng</language><publisher>Netherlands: Elsevier Ireland Ltd</publisher><subject>Adult ; Aged ; Asian Continental Ancestry Group - genetics ; Cardiovascular ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - epidemiology ; Diabetes Mellitus, Type 2 - genetics ; Diabetic Angiopathies - blood ; Diabetic Angiopathies - epidemiology ; Diabetic Angiopathies - genetics ; Diabetic macrovascular disease ; Female ; Genetic risk score ; Humans ; Hyperuricemia - blood ; Hyperuricemia - epidemiology ; Male ; Mendelian randomization analysis ; Mendelian Randomization Analysis - methods ; Microvessels - metabolism ; Microvessels - pathology ; Middle Aged ; Polymorphism, Single Nucleotide - genetics ; Single nucleotide polymorphism ; Uric acid ; Uric Acid - blood</subject><ispartof>International journal of cardiology, 2016-07, Vol.214, p.194-199</ispartof><rights>2016 Elsevier Ireland Ltd</rights><rights>Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c562t-b0d59b68bb5ab4147280a202fbe754f36fd7bbb6729ad8bffeb2e8624f69c75e3</citedby><cites>FETCH-LOGICAL-c562t-b0d59b68bb5ab4147280a202fbe754f36fd7bbb6729ad8bffeb2e8624f69c75e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27064641$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yan, Dandan</creatorcontrib><creatorcontrib>Wang, Jie</creatorcontrib><creatorcontrib>Jiang, Feng</creatorcontrib><creatorcontrib>Zhang, Rong</creatorcontrib><creatorcontrib>Wang, Tao</creatorcontrib><creatorcontrib>Wang, Shiyun</creatorcontrib><creatorcontrib>Peng, Danfeng</creatorcontrib><creatorcontrib>He, Zhen</creatorcontrib><creatorcontrib>Chen, Haibing</creatorcontrib><creatorcontrib>Bao, Yuqian</creatorcontrib><creatorcontrib>Hu, Cheng</creatorcontrib><creatorcontrib>Jia, Weiping</creatorcontrib><title>A causal relationship between uric acid and diabetic macrovascular disease in Chinese type 2 diabetes patients: A Mendelian randomization analysis</title><title>International journal of cardiology</title><addtitle>Int J Cardiol</addtitle><description>Abstract Background As the association between uric acid and macrovascular disease has been heavily debated, we aimed to confirm whether there is a causal relationship between uric acid and diabetic macrovascular disease through Mendelian randomization analysis. Methods In 3207 type 2 diabetes patients, seventeen SNPs (single nucleotide polymorphisms) related to uric acid were genotyped. A weighted GRS (genetic risk score) was calculated using selected SNPs and the strength of their effects on uric acid levels. Diabetic macrovascular disease was diagnosed through vascular ultrasound, magnetic resonance imaging or other clinical evidence. Associations of diabetic macrovascular disease with uric acid and weighted GRS were evaluated separately. Results In total participants and among females, the prevalence of diabetic macrovascular disease was significantly higher in hyperuricemic group than in normouricemic group, and uric acid was associated with diabetic macrovascular disease (OR = 1.068, p = 0.0349; OR = 1.122, p = 0.0158). The prevalence of diabetic macrovascular disease increased with the weighted GRS in a J-shaped manner for the females. The weighted GRS was positively correlated with uric acid in total population, male patients and female patients (β = 0.203, p &lt; 0.0001; β = 0.255, p &lt; 0.0001; β = 0.142, p &lt; 0.0001, respectively). The weighted GRS was significantly associated with diabetic macrovascular disease in female patients (OR = 1.184, p = 0.0039). Among females, the observed association between weighted GRS and diabetic macrovascular disease was greater than predicted. 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Methods In 3207 type 2 diabetes patients, seventeen SNPs (single nucleotide polymorphisms) related to uric acid were genotyped. A weighted GRS (genetic risk score) was calculated using selected SNPs and the strength of their effects on uric acid levels. Diabetic macrovascular disease was diagnosed through vascular ultrasound, magnetic resonance imaging or other clinical evidence. Associations of diabetic macrovascular disease with uric acid and weighted GRS were evaluated separately. Results In total participants and among females, the prevalence of diabetic macrovascular disease was significantly higher in hyperuricemic group than in normouricemic group, and uric acid was associated with diabetic macrovascular disease (OR = 1.068, p = 0.0349; OR = 1.122, p = 0.0158). The prevalence of diabetic macrovascular disease increased with the weighted GRS in a J-shaped manner for the females. 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source ScienceDirect Journals
subjects Adult
Aged
Asian Continental Ancestry Group - genetics
Cardiovascular
Cross-Sectional Studies
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - epidemiology
Diabetes Mellitus, Type 2 - genetics
Diabetic Angiopathies - blood
Diabetic Angiopathies - epidemiology
Diabetic Angiopathies - genetics
Diabetic macrovascular disease
Female
Genetic risk score
Humans
Hyperuricemia - blood
Hyperuricemia - epidemiology
Male
Mendelian randomization analysis
Mendelian Randomization Analysis - methods
Microvessels - metabolism
Microvessels - pathology
Middle Aged
Polymorphism, Single Nucleotide - genetics
Single nucleotide polymorphism
Uric acid
Uric Acid - blood
title A causal relationship between uric acid and diabetic macrovascular disease in Chinese type 2 diabetes patients: A Mendelian randomization analysis
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