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Acta Diabetologica
Published in: Acta Diabetologica 1/2024

05-09-2023 | Hypertension | Original Article

Associations of CKIP-1 and LOX-1 polymorphisms with the risk of type 2 diabetes mellitus with hypertension among Chinese adults

Authors: Jiajie Xiong, Liu Zhang, Guimei Chen, Pu Dong, Jiani Tong, Long Hua, Ning Li, Liying Wen, Lijun Zhu, Weiwei Chang, Yuelong Jin

Published in: Acta Diabetologica | Issue 1/2024

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Abstract

Aims

Type 2 diabetes mellitus (T2DM) and hypertension are common high-incidence diseases, closely related, and have common pathogenic basis such as oxidative stress. Casein kinase 2 interacting protein-1 (CKIP-1) and low-density lipoprotein receptor (LOX-1) are considered to be important factors affect the level of oxidative stress in the body. The main purpose of this study was to explore the relationship between CKIP-1 (rs6693817 A > T, rs2306235 C > G) and LOX-1 (rs1050283 G > A, rs11053646 C > G) polymorphisms and the risk of hypertension and diabetes, and try to find new candidate genes for diabetes and diabetes with hypertension etiology in Chinese population.

Methods

574 T2DM patients and 597 controls frequently matched by age and sex were selected for genotyping of CKIP-1 (rs6693817 A > T, rs2306235 C > G) and LOX-1 gene (rs1050283 G > A, rs11053646 C > G). Logistic regression was used to analyze the correlation between different genotypes and the risk of T2DM and T2DM with hypertension, and the results were expressed as odds ratio (OR) and 95% confidence interval (95% CI).

Results

We found that the risk of T2DM in the AA + AT genotype of rs6693817 was higher than that in the TT genotype in Chinese population (OR = 1.318, 95%CI: 1.011–1.717, P = 0.041), and the difference was still significant after adjustment (OR = 1.370, 95%CI: 1.043–1.799, Padjusted = 0.024), the difference of heterozygotes (AT vs TT: OR = 1.374, 95%CI: 1.026–1.840, Padjusted = 0.033) was statistically significant. But after Bonferroni correction, the significance of the above sites disappeared. And rs6693817 was associated with the risk of T2DM combined with hypertension before and after adjustment in dominant model (OR = 1.424, 95% CI: 1.038–1.954, P = 0.028; OR = 1.460, 95% CI: 1.057–2.015, Padjusted = 0.021, respectively) and in heterozygote model (OR = 1.499, 95% CI: 1.069–2.102, P = 0.019; OR = 1.562, 95% CI: 1.106–2.207, Padjusted = 0.011, respectively). However, only the statistical significance of the heterozygous model remained after Bonferroni correction. rs2306235, rs1050283 and rs11053646 were not significantly correlated with T2DM and T2DM combined with hypertension risk (P > 0.05).

Conclusions

The results suggest that CKIP-1 rs6693817 is related to the susceptibility of Chinese people to T2DM with hypertension, providing a new genetic target for the treatment of diabetes with hypertension with in the future.
Appendix
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Literature
1.
Roth GA, Mensah GA, Johnson CO et al (2020) Global burden of cardiovascular diseases and risk factors, 1990–2019: update from the GBD 2019 study. J Am Coll Cardiol 76(25):2982–3021PubMedPubMedCentralCrossRef
2.
3.
China Cardiovascular Health and Disease Report 2020 Official publication. Chin J Cardiol 2021, 26(3):276 (in Chinese)
4.
Wang N, Yang X, Dai GH, Ma T, Zhang CB (2023) Subgroup analysis of endpoint events in patients with myocardial infarction during follow-up: retrospective cohort study. Chin J Integr Tradit West Med 1–9 (in Chinese)
5.
Perrone L, Valente M (2021) The emerging role of metabolism in brain-heart axis: new challenge for the therapy and prevention of Alzheimer disease. May thioredoxin interacting protein (TXNIP) play a role? Biomolecules 11(11):1652PubMedPubMedCentralCrossRef
6.
Yusuf S, Joseph P, Rangarajan S et al (2020) Modifiable risk factors, cardiovascular disease, and mortality in 155722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study. Lancet 395(10226):795–808PubMedCrossRef
7.
Yu ZQ (2023) Prevention and treatment of heart failure from the perspective of hypertension: diagnosis of patients with hypertensive heart failure. Rural Med China 30(1):4–7 ((in Chinese))
8.
International Hypoglycaemia Study G (2019) Hypoglycaemia, cardiovascular disease, and mortality in diabetes: epidemiology, pathogenesis, and management. Lancet Diabetes Endocrinol 7(5):385–396CrossRef
9.
Lee SW, Kim HC, Lee JM, Yun YM, Lee JY, Suh I (2017) Association between changes in systolic blood pressure and incident diabetes in a community-based cohort study in Korea. Hypertens Res 40(7):710–716PubMedCrossRef
10.
11.
Ferrannini E, Cushman WC (2012) Diabetes and hypertension: the bad companions. Lancet 380(9841):601–610PubMedCrossRef
12.
Song J, Sheng CS, Huang QF et al (2016) Management of hypertension and diabetes mellitus by cardiovascular and endocrine physicians: a China registry. J Hypertens 34(8):1648–1653PubMedPubMedCentralCrossRef
13.
Kamalumpundi V, Shams E, Tucker C et al (2022) Mechanisms and pharmacotherapy of hypertension associated with type 2 diabetes. Biochem Pharmacol 206:115304PubMedCrossRef
14.
Yildiz M, Esenboga K, Oktay AA (2020) Hypertension and diabetes mellitus: highlights of a complex relationship. Curr Opin Cardiol 35(4):397–404PubMedCrossRef
15.
Yamazaki D, Hitomi H, Nishiyama A (2018) Hypertension with diabetes mellitus complications. Hypertens Res 41(3):147–156PubMedCrossRef
16.
Regine I, Husain R, Aswathi RP, Reddy DR, Ahmed S, Ramakrishnan V (2020) Association between PPARgammars1801282 polymorphism with diabetic nephropathy and type-2 diabetes mellitus susceptibility in south India and a meta-analysis. Nefrologia (Engl Ed) 40(3):287–298PubMedCrossRef
17.
Meng Y, Liu X, Ma K et al (2019) Association of MTHFR C677T polymorphism and type 2 diabetes mellitus (T2DM) susceptibility. Mol Genet Genomic Med 7(12):e1020PubMedPubMedCentralCrossRef
18.
Demikhova N, Mazur T (2019) The correlation between polymorphism of Cyp7A1 gene and index of left ventricular mass for hypertensive patients with diabetic nephropathy. Atherosclerosis 287:e123CrossRef
19.
Liu X (2022) Study on the relationship between atherosclerosis related gene polymorphism and genetic susceptibility to lower limb arterial disease in type 2 diabetes doctor. Hebei Medical University (in Chinese)
20.
Huang X, Ma L, Wang X et al (2022) Ckip-1 mediates P. gingivalis-suppressed cementoblast mineralization. J Dent Res 101(5):599–608PubMedCrossRef
21.
Yang Y, Xiao H, Lin Z et al (2022) The ubiquitination of CKIP-1 mediated by Src aggravates diabetic renal fibrosis (original article). Biochem Pharmacol 206:115339PubMedCrossRef
22.
Gong W, Chen C, Xiong F et al (2016) CKIP-1 ameliorates high glucose-induced expression of fibronectin and intercellular cell adhesion molecule-1 by activating the Nrf2/ARE pathway in glomerular mesangial cells. Biochem Pharmacol 116:140–152PubMedCrossRef
23.
Fan J, Liu L, Liu Q et al (2019) CKIP-1 limits foam cell formation and inhibits atherosclerosis by promoting degradation of Oct-1 by REGgamma. Nat Commun 10(1):425PubMedPubMedCentralCrossRef
24.
Fu L, Zhang L (2019) Physiological functions of CKIP-1: from molecular mechanisms to therapy implications. Ageing Res Rev 53:100908PubMedCrossRef
25.
Fan J (2017) Study on the function and molecular mechanism of CKIP-1 in atherosclerosis and megakaryocyte differentiation doctor. Acad Milit Med Sci (in Chinese)
26.
Li MP, Zhang YJ, Hu XL et al (2017) Association of CKIP-1 P21A polymorphism with risk of chronic heart failure in a Chinese population. Oncotarget 8(22):36545–36552PubMedPubMedCentralCrossRef
27.
Yao SJ, Lan TH, Zhang XY et al (2023) LOX-1 regulation in anti-atherosclerosis of active compounds of herbal medicine: current knowledge and the new insight. Chin J Integr Med 29(2):179–185PubMedCrossRef
28.
Chistiakov DA, Orekhov AN, Bobryshev YV (2016) LOX-1-mediated effects on vascular cells in atherosclerosis. Cell Physiol Biochem 38(5):1851–1859PubMedCrossRef
29.
Roumeliotis S, Roumeliotis A, Georgianos PI et al (2021) Oxidized LDL is associated with eGFR decline in proteinuric diabetic kidney disease: a cohort study. Oxid Med Cell Longev
30.
Islam J, Lee HJ, Yang SH et al (2020) Expansion of myeloid-derived suppressor cells correlates with renal progression in type 2 diabetic nephropathy. Immune Netw 20(2):e18PubMedPubMedCentralCrossRef
31.
Dominguez JH, Mehta JL, Li D et al (2008) Anti-LOX-1 therapy in rats with diabetes and dyslipidemia: ablation of renal vascular and epithelial manifestations. Am J Physiol Renal Physiol 294(1):F110-119PubMedCrossRef
32.
Li Y, Duan Z, Gao D, Huang S, Yuan H, Niu X (2012) The new role of LOX-1 in hypertension induced neuronal apoptosis. Biochem Biophys Res Commun 425(4):735–740PubMedCrossRef
33.
Chang WW, Wen LY, Zhang L, Tong X, Jin YL, Chen GM (2022) Association of rs2910164 in miR-146a with type 2 diabetes mellitus: a case-control and meta-analysis study. Front Endocrinol (Lausanne) 13:961635PubMedCrossRef
34.
Consensus of Experts on the Prevention and Treatment of Adult Obesity in China. Chin J Endocrinol Metab 2011; 09:711–717 (in Chinese)
35.
Chang WW, Zhang L, Wen LY et al (2023) Association of tag single nucleotide polymorphisms (SNPs) at lncRNA MALAT1 with type 2 diabetes mellitus susceptibility in the Chinese Han population: a case–control study. Gene 851:147008PubMedCrossRef
36.
Curtin F, Schulz P (1998) Multiple correlations and Bonferroni’s correction. Biol Psychiatry 44(8):775–777PubMedCrossRef
37.
Liu W, Lu L, Pan H et al (2022) Heme oxygenase-1 and hemopexin gene polymorphisms and the risk of anti-tuberculosis drug-induced hepatotoxicity in China. Pharmacogenomics 23(7):431–441PubMedCrossRef
38.
Wang YW (2014) Research on the function and regulatory mechanism of CKIP-1 in macrophage proliferation and polarization doctor Chinese People's liberation army academy of military medical sciences (in Chinese)
39.
Liu DC (2014) The association between AKT2 gene polymorphism and coronary heart disease with diabetes in northern China. Master, Jilin University (in Chinese)
40.
41.
Gao Q, Ma E, Chen J et al (2022) Qingda granule prevents obesity-induced hypertension and cardiac dysfunction by inhibiting adverse Akt signaling activation. Heliyon 8(12):e12099PubMedPubMedCentralCrossRef
42.
Zhao X, Wang J, Li P, Tang L, Bai Y (2021) Casein kinase 2-interacting protein-1 alleviates high glucose-reduced autophagy, oxidative stress, and apoptosis in retinal pigment epithelial cells via activating the p62/KEAP1/NRF2 signaling pathway. J Ophthalmol 2021:6694050PubMedPubMedCentralCrossRef
43.
Chen SM, Hu YJ, Yan WR et al (2023) Construction and evaluation of rat model of streptozotocin induced diabetes encephalopathy. Res Tissue Eng China 1–5 (in Chinese)
44.
Huang Y, Zhang J, Xu D, Peng Y, Jin Y, Zhang L (2021) SIRT6-specific inhibitor OSS-128167 exacerbates diabetic cardiomyopathy by aggravating inflammation and oxidative stress. Mol Med Rep 23(5):367PubMedPubMedCentralCrossRef
45.
Barrows IR, Ramezani A, Raj DS (2019) Inflammation, immunity, and oxidative stress in hypertension-partners in crime? Adv Chronic Kidney Dis 26(2):122–130PubMedPubMedCentralCrossRef
46.
Jia X, Gao X, Li X et al (2023) Demonstration of safety characteristics and effects on gut microbiota of Lactobacillus gasseri HMV18. Food Sci Hum Wellness 1–21
47.
Zheng J (2013) An association study between BSG and CKIP-1 gene polymorphisms and susceptibility to chronic congestive heart failure in Chinese Han population. Doctor, Central South University (in Chinese)
48.
Li MP, Zhou JP, Sun T et al (2011) Genetic susceptibility of CKIP-1 rs2306235 polymorphism to chronic heart failure In: Inheritance and development, creating a new high in the cause of physiological sciences in Hunan Province-2011 Academic Annual Meeting of the Hunan Physiological Science Association. Changsha, Hunan, China, 22–23 (in Chinese)
49.
Yang X, Yao W, Liu H, Gao Y, Liu R, Xu L (2017) Tangluoning, a traditional Chinese medicine, attenuates in vivo and in vitro diabetic peripheral neuropathy through modulation of PERK/Nrf2 pathway. Sci Rep 7(1):1014PubMedPubMedCentralCrossRef
50.
Dong Y, Xing Y, Sun J, Sun W, Xu Y, Quan C (2020) Baicalein alleviates liver oxidative stress and apoptosis induced by high-level glucose through the activation of the PERK/Nrf2 signaling pathway. Molecules 25(3):599PubMedPubMedCentralCrossRef
51.
Zhuang WW (2022) Study on the mechanism of Nrf2 regulating LOX-1 pathway in the proliferation and migration of atherosclerotic vascular smooth muscle cells. Master, Yangzhou university (in Chinese)
52.
Jaganjac M, Milkovic L, Gegotek A et al (2020) The relevance of pathophysiological alterations in redox signaling of 4-hydroxynonenal for pharmacological therapies of major stress-associated diseases. Free Radic Biol Med 157:128–153PubMedCrossRef
53.
Huo CJ, Yu XJ, Sun YJ et al (2020) Irisin lowers blood pressure by activating the Nrf2 signaling pathway in the hypothalamic paraventricular nucleus of spontaneously hypertensive rats. Toxicol Appl Pharmacol 394:114953PubMedCrossRef
54.
Arcambal A, Taile J, Couret D et al (2020) Protective effects of antioxidant polyphenols against hyperglycemia-mediated alterations in cerebral endothelial cells and a mouse stroke model. Mol Nutr Food Res 64(13):e1900779PubMedCrossRef
55.
Zhang Q (2019) Correlation analysis between LOX-1, LAL and ACAT1 single nucleotide polymorphisms and carotid atherosclerosis in Han population in northern China. Master, China Medical University (in Chinese)
56.
Salehipour P, Rezagholizadeh F, Mahdiannasser M, Kazerani R, Modarressi MH (2021) Association of OLR1 gene polymorphisms with the risk of coronary artery disease: a systematic review and meta-analysis. Heart Lung 50(2):334–343PubMedCrossRef
57.
Wang ZT, Zhong XL, Tan MS et al (2018) Association of lectin-like oxidized low density lipoprotein receptor 1 (OLR1) polymorphisms with late-onset Alzheimer disease in Han Chinese. Ann Transl Med 6(10):172PubMedPubMedCentralCrossRef
58.
Guo X, Xiang Y, Yang H, Yu L, Peng X, Guo R (2017) Association of the LOX-1 rs1050283 polymorphism with risk for atherosclerotic cerebral infarction and its effect on sLOX-1 and LOX-1 expression in a Chinese population. J Atheroscler Thromb 24(6):572–582PubMedPubMedCentralCrossRef
59.
Predazzi IM, Norata GD, Vecchione L et al (2012) Association between OLR1 K167N SNP and intima media thickness of the common carotid artery in the general population. PLoS ONE 7(2):e31086PubMedPubMedCentralCrossRef
60.
Paquette M, Dufour R, Baass A (2017) Scavenger receptor LOX1 genotype predicts coronary artery disease in patients with familial hypercholesterolemia. Can J Cardiol 33(10):1312–1318PubMedCrossRef
Metadata
Title
Associations of CKIP-1 and LOX-1 polymorphisms with the risk of type 2 diabetes mellitus with hypertension among Chinese adults
Authors
Jiajie Xiong
Liu Zhang
Guimei Chen
Pu Dong
Jiani Tong
Long Hua
Ning Li
Liying Wen
Lijun Zhu
Weiwei Chang
Yuelong Jin
Publication date
05-09-2023
Publisher
Springer Milan
Published in
Acta Diabetologica / Issue 1/2024
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-023-02175-z

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