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An eQTL variant of ALDH1A2 is associated with Kashin-Beck disease in Chinese population

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Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Introduction

The aims of the study were to investigate the relationship between aldehyde dehydrogenase 1 family member A2 (ALDH1A2) and Kashin-Beck disease (KBD), explore the effects of the rs3204689 polymorphism and methylation status on the expression levels of ALDH1A2, and further clarify the pathogenesis of KBD.

Materials and methods

The genotype of ALDH1A2 rs3204689 was detected by PCR–RFLP in 103 KBD patients and 109 healthy controls in the whole blood. The mRNA level of ALDH1A2 was measured by qRT-PCR, and the protein expression was detected using IHC staining and Western blotting. The MSP-PCR was used to identify the ALDH1A2 methylation level.

Results

There were significant differences in G/G, G/C, and C/C frequencies of ALDH1A2 rs3204689 between the KBD and control groups (χ2 = 7.113, P = 0.029); the minor allele G of ALDH1A2 was associated with the risk of KBD (χ2 = 5.984, P = 0.014). The mRNA and protein levels of ALDH1A2 were increased in the whole blood and cartilage of KBD patients compared with the controls (P = 0.049, P < 0.0001, P = 0.019). Meanwhile, a statistically significant difference was observed between G/G, G/C and C/C genotype on mRNA expression (P = 0.039). The methylation level of the ALDH1A2 gene promoter region showed no significant difference between the KBD and control groups (χ2 = 0.317, P = 0.573).

Conclusion

Our case–control study indicates that the common variant rs3204689 near ALDH1A2 is associated with KBD in Chinese population. The risk allele G of rs3204689 is statistically linked to the high expression of ALDH1A2, which is up-regulated in the cartilage and whole blood of KBD patients. Our findings suggest a potential role of ALDH1A2 in the pathogenesis of KBD.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (81773372, 82073494, 81573104), and the Graduate Innovation Experiment Center of Xi’an Jiaotong University (YJSCX-2018-015).

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Author notes

  1. Di Zhang and Qiang Li contributed equally to this work.

Authors and Affiliations

  1. Institute of Endemic Diseases and Key Laboratory of Trace Elements and Endemic Diseases, School of Public Health, National Health Commission of the People’s Republic of China, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, Shaanxi, People’s Republic of China

    Di Zhang, Qiang Li, Dandan Zhang, Xiaoli Yang, Chen Wang, Rongqiang Zhang, Xuena Yang, Zhaofang Li & Yongmin Xiong

  2. Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China

    Rongqiang Zhang

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  1. Di Zhang
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Correspondence to Yongmin Xiong.

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Zhang, D., Li, Q., Zhang, D. et al. An eQTL variant of ALDH1A2 is associated with Kashin-Beck disease in Chinese population. J Bone Miner Metab 40, 317–326 (2022). https://doi.org/10.1007/s00774-021-01287-2

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  • DOI: https://doi.org/10.1007/s00774-021-01287-2

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