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

Dandan Yan; Jie Wang; Feng Jiang; Rong Zhang; Tao Wang; Shiyun Wang; Danfeng Peng; Zhen He; Haibing Chen; Yuqian Bao; Cheng Hu; Weiping Jia

doi:10.1016/j.ijcard.2016.03.206

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

Int J Cardiol. 2016 Jul 1:214:194-9. doi: 10.1016/j.ijcard.2016.03.206. Epub 2016 Mar 31.

Authors

Dandan Yan¹, Jie Wang¹, Feng Jiang¹, Rong Zhang¹, Tao Wang¹, Shiyun Wang¹, Danfeng Peng¹, Zhen He¹, Haibing Chen¹, Yuqian Bao¹, Cheng Hu², Weiping Jia¹

Affiliations

¹ Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
² Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China; Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai 201499, China. Electronic address: [email protected].

PMID: 27064641
DOI: 10.1016/j.ijcard.2016.03.206

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.

Keywords: Diabetic macrovascular disease; Genetic risk score; Mendelian randomization analysis; Single nucleotide polymorphism; Uric acid.

MeSH terms

Adult
Aged
Asian People* / genetics
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
Female
Humans
Hyperuricemia / blood
Hyperuricemia / epidemiology
Male
Mendelian Randomization Analysis / methods*
Microvessels / metabolism
Microvessels / pathology
Middle Aged
Polymorphism, Single Nucleotide / genetics
Uric Acid / blood*

Substances

Uric Acid