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

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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.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12933-022-01702-6.

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Author and article information

Contributors

Weiping Jia:

ORCID: http://orcid.org/0000-0002-6244-2168

wpjia@sjtu.edu.cn

Cheng Hu:

ORCID: http://orcid.org/0000-0003-4314-2386

alfredhc@sjtu.edu.cn

Journal

Journal ID (nlm-ta): Cardiovasc Diabetol

Journal ID (iso-abbrev): Cardiovasc Diabetol

Title: Cardiovascular Diabetology

Publisher: BioMed Central (London )

ISSN (Electronic): 1475-2840

Publication date (Electronic): 2 December 2022

Publication date PMC-release: 2 December 2022

Publication date Collection: 2022

Volume: 21

Electronic Location Identifier: 265

Affiliations

[1 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, 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, ; 600 Yishan Road, Shanghai, 200233 People’s Republic of China

[2 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, 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, ; 600 Yishan Road, Shanghai, 200233 People’s Republic of China

[3 ]Institute for Metabolic Disease, Fengxian Central Hospital Affiliated to Southern Medical University, 6600 Nanfeng Road, 201499 Shanghai, People’s Republic of China

Author information

Weiping Jia http://orcid.org/0000-0002-6244-2168

Cheng Hu http://orcid.org/0000-0003-4314-2386

Article

Publisher ID: 1702

DOI: 10.1186/s12933-022-01702-6

PMC ID: 9716717

SO-VID: fe19b502-2f88-4c6d-b641-bac2574cfde2

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 12 August 2022

Date accepted : 21 November 2022

Funding

Funded by: National Natural Science Foundation of China

Award ID: 82000772

Award ID: 81974118

Funded by: Shanghai Sailing Program

Award ID: 20YF1435700

Funded by: Shuguang Project

Award ID: 21SG11

Funded by: Shanghai Outstanding Academic Leaders

Award ID: 20XD1433300

Funded by: Innovative research team of high-level local universities in Shanghai

Award ID: SHSMU-ZDCX20212700

Custom metadata

ScienceOpen disciplines: Endocrinology & Diabetes

Keywords: haptoglobin,dimethylarginine dimethylaminohydrolase,asymmetric dimethylarginine,single nucleotide polymorphism,diabetic macroangiopathy

Data availability: