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. 2025 Aug;21(4):695-707.
doi: 10.1007/s11302-024-10004-3. Epub 2024 May 17.

CD73 polymorphisms are associated with schizophrenia

He-Xia Peng #  1   2 , Li-Li Zhang #  1   2 , Dan Jiang #  1   2 , Na Jian  1   2 , Ting-Mei Zhang  1   2 , Jia-Guo Luo  3   4 , Hai-Yan Yin  5   6
Affiliations

CD73 polymorphisms are associated with schizophrenia

He-Xia Peng et al. Purinergic Signal. 2025 Aug.

Abstract

Ecto-5'-nucleotidase/CD73 enzyme plays a key role in the regulation of extracellular adenosine levels, thereby exerting influence on adenosine homeostasis. Emerging evidence suggests that perturbations in purines and ecto-5'-nucleotidase activity are associated with an augmented susceptibility to schizophrenia. However, the precise impact of genetic variations in CD73 on individuals with schizophrenia remains poorly understood. Here, our study demonstrated that rs3734442 allele and rs4431401 heterozygote were conferred a significant risk of schizophrenia disease (rs3734442: odds ratio, 0.556; 95% CI, 0.375 to 0.825; p = 0.004; rs4431401: odds ratio, 1.881, 95% CI, 1.117 to 3.166; p = 0.020). Comparing different genders, we observed a significant association between rs3734442 genotypes and male cases (rs3734442: odds ratio, 0.452; 95% CI, 0.257 to 0.796; p = 0.007). Likewise, there was a significant association between rs4431401 genotypes and male patients (rs4431401: odds ratio, 2.570; 95% CI, 1.196 to 5.522; p = 0.015). Based on family history and antipsychotics medication usage, our data reveals that the rs9444348 allele exhibits the most significant association with familial susceptibility to schizophrenia (odds ratio, 1.541; 95% CI, 1.009 to 2.353; p = 0.048 for A vs G). Moreover, individuals carrying variants of rs6922, rs2229523, and rs2065114 while being treated with clozapine demonstrate a higher frequency proportion compared to those receiving risperidone treatment (p = 0.035; p = 0.049; p = 0.027 respectively). Additionally, our results indicate that patients with GG genotype of rs9444348 had significantly higher likelihood of using clozapine instead of sulpiride (p = 0.048). Overall, our data strongly suggest that genetic variations in CD73 are significantly associated with schizophrenia risk and may serve as valuable resources for identifying therapeutic targets.

Keywords: CD73; Ecto-5’-nucleotidase; Schizophrenia; Single-nucleotide polymorphism.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Ethical approval: The studies involving human participants were reviewed and approved by the Ethics Committee of Chengdu Jinxin Mental Diseases Hospital in Sichuan Province, China. All procedures performed in this study were in accordance with the 1964 Declaration of Helsinki and its later amendments. Informed consent: The patients provided their written informed consent to participate in this study.

Figures

Fig. 1
Fig. 1
Linkage disequilibrium of CD73 SNPs loci
See this image and copyright information in PMC

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