The effect of haptoglobin genotype on the association of asymmetric dimethylarginine and DDAH 1 polymorphism with diabetic macroangiopathy

Shiyun Wang; Zixuan Deng; Hong Zhang; Rong Zhang; Dandan Yan; Xiaojiao Zheng; Weiping Jia; Cheng Hu

doi:10.1186/s12933-022-01702-6

Cardiovascular Diabetology (Dec 2022)

The effect of haptoglobin genotype on the association of asymmetric dimethylarginine and DDAH 1 polymorphism with diabetic macroangiopathy

Shiyun Wang,
Zixuan Deng,
Hong Zhang,
Rong Zhang,
Dandan Yan,
Xiaojiao Zheng,
Weiping Jia,
Cheng Hu

Affiliations

Shiyun Wang: Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes
Zixuan Deng: Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes
Hong Zhang: Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes
Rong Zhang: Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes
Dandan Yan: Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes
Xiaojiao Zheng: Center for Translational Medicine, Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Weiping Jia: Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes
Cheng Hu: Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes

DOI: https://doi.org/10.1186/s12933-022-01702-6
Journal volume & issue: Vol. 21, no. 1
pp. 1 – 9

Abstract

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Abstract Background Dimethylarginine dimethylaminohydrolase (DDAH) 1 maintains the bioavailability of nitric oxide by degrading asymmetric dimethylarginine (ADMA). Here, we aimed to investigate the effect of haptoglobin (Hp) genotype on the association of ADMA and DDAH 1 polymorphism with diabetic macroangiopathy. Methods In stage 1, 90 Chinese participants with type 2 diabetes were enrolled to measure a panel of targeted metabolites, including ADMA, using tandem mass spectrometry (BIOCRATES AbsoluteIDQ™ p180 kit). In stage 2, an independent cohort of 2965 Chinese patients with type 2 diabetes was recruited to analyze the effect of Hp genotype on the association between DDAH 1 rs233109 and diabetic macroangiopathy. Hp genotypes were detected using a validated assay based on the TaqMan method. DDAH 1 rs233109 was genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy using the MassARRAY platform. Results In stage 1, serum ADMA levels correlated with common Hp genotypes (β ± SE = − 0.049 ± 0.023, P = 0.035), but not with diabetic macroangiopathy (P = 0.316). In stage 2, the distribution of DDAH 1 rs233109 genotype frequencies was 15% (CC), 47% (TC), and 38% (TT), which was in Hardy-Weinberg equilibrium (P = 0.948). A significant Hp genotype by rs 233109 genotype interaction effect on diabetic macroangiopathy was found (P = 0.017). After adjusting for confounders, patients homozygous for rs233109 CC were more likely to develop diabetic macroangiopathy than those carrying TT homozygotes in the Hp 2-2 subgroup [odds ratio = 1.750 (95% confidence interval, 1.101–2.783), P = 0.018]. Conclusion Hp genotype affects the association between DDAH 1 rs233109 and diabetic macroangiopathy in Chinese patients with type 2 diabetes.

Published in Cardiovascular Diabetology

ISSN: 1475-2840 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system
Website: https://cardiab.biomedcentral.com/

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