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

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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.

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Data availability

The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

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Acknowledgements

Gratitude was given to all participants and contributors who had participated in this study. The authors would also like to thank the editors of this manuscript.

Funding

This project was supported by Grants from the National Natural Science Foundation of China (82003546), the Anhui Natural Science Foundation (1808085MH297;1808085QH252), Anhui Province Excellent Young Talents Fund Program of Higher Education Institutions (gxgnfx2022039), and Talents Program for Academic Leaders and Reserve Candidates of Wannan Medical College (No. School Administration Letter [2021] No. 46).

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Author notes

  1. Jiajie Xiong, Liu Zhang and Guimei Chen have contributed equally to this work.

Authors and Affiliations

  1. Department of Epidemiology and Health Statistics, School of Public Health, Wannan Medical College, Wuhu, 241002, Anhui, China

    Jiajie Xiong, Pu Dong, Jiani Tong, Long Hua, Ning Li, Liying Wen, Lijun Zhu, Weiwei Chang & Yuelong Jin

  2. Department of Hospital Infection Management Office, Wuhu Hospital of Traditional Chinese Medicine, Wuhu, 241000, Anhui, China

    Liu Zhang

  3. School of Health Management, Anhui Medical University, Hefei, 230032, Anhui, China

    Guimei Chen

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  1. Jiajie Xiong
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Contributions

CWW and JYL designed the study. XJJ, TJN, LN, and HL contributed to literature searching, data collection and analysis. CWW and JYL assessed study quality. XJJ, ZL and CGM wrote the manuscript. WLY and ZLJ revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Weiwei Chang or Yuelong Jin.

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Xiong, J., Zhang, L., Chen, G. et al. Associations of CKIP-1 and LOX-1 polymorphisms with the risk of type 2 diabetes mellitus with hypertension among Chinese adults. Acta Diabetol 61, 43–52 (2024). https://doi.org/10.1007/s00592-023-02175-z

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