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Introduction <p>AXIN1 (axis inhibition protein&#xa0;1), as a rate-limiting component of canonical Wingless-type mouse mammary tumor virus integration site (Wnt)/β-catenin signaling pathway, may influence midbrain dopaminergic neurons. A recent genome-wide association study identified <i>AXIN1</i> as a candidate gene for Parkinson’s disease (PD). Our study aimed to investigate the potential relevance of <i>AXIN1</i> single nucleotide polymorphisms (rs13337493 and rs9921222) in the risk, clinical characteristics, and pathology of PD.</p> Methods <p>Data were collected from the Northern Han Chinese and Parkinson’s Progression Markers Initiative (PPMI) cohorts. Associations between <i>AXIN1</i> variants, PD-related biomarkers, and clinical manifestations were analyzed.</p> Results <p>Both loci were identified as risk factors in the Northern Han Chinese population, and the A&#xa0;allele of rs13337493 [odds ratio (OR) 1.320, 95% confidence interval (CI) 1.052, 1.653, <i>P</i><sub>c</sub> = 0.036] and the T&#xa0;allele of rs9921222 (OR 1.351, 95%&#xa0;CI 1.045, 1.747, <i>P</i><sub>c</sub> = 0.042) showed increased susceptibility to PD. The risk effect of rs9921222 was predominant in the male cohort (OR 1.504, 95%&#xa0;CI 1.058, 2.139, <i>P</i><sub>c</sub> = 0.044). Rs13337493 was related to worse motor function in white individuals, which was represented by the Hoehn &amp; Yahr stage (OR 2.775, 95%&#xa0;CI 1.195, 6.447, <i>P</i><sub>c</sub> = 0.036). It also correlated with compensatory elevation of cerebrospinal fluid (CSF) 3,4-dihydroxyphenylalanine (DOPA, <i>β</i> = 0.040, 95%&#xa0;CI 0.007, 0.073, <i>P</i><sub>c</sub> = 0.038).</p> Conclusion <p>Our findings support a gatekeeper role for <i>AXIN1</i>; its polymorphisms contribute to increased PD&#xa0;susceptibility and accelerated motor progression, yet may also trigger a compensatory presynaptic response, as evidenced by elevated CSF DOPA levels, to counteract neurodegeneration. Future studies should include larger sample sizes, more diverse ethnic populations, and protein-level investigations.</p>

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AXIN1 Polymorphisms Potentially Modulate Parkinson’s Disease Susceptibility: A Cross-Sectional Study in Northern Han Chinese and White Populations

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月5日

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  • Zhen Kong,
  • Ran Yu,
  • Chengqian Li,
  • Qiqing He,
  • Yuting Zhou,
  • Xue Zhang,
  • Yaqing Li,
  • Anmu Xie,
  • Binghui Hou

摘要

Introduction

AXIN1 (axis inhibition protein 1), as a rate-limiting component of canonical Wingless-type mouse mammary tumor virus integration site (Wnt)/β-catenin signaling pathway, may influence midbrain dopaminergic neurons. A recent genome-wide association study identified AXIN1 as a candidate gene for Parkinson’s disease (PD). Our study aimed to investigate the potential relevance of AXIN1 single nucleotide polymorphisms (rs13337493 and rs9921222) in the risk, clinical characteristics, and pathology of PD.

Methods

Data were collected from the Northern Han Chinese and Parkinson’s Progression Markers Initiative (PPMI) cohorts. Associations between AXIN1 variants, PD-related biomarkers, and clinical manifestations were analyzed.

Results

Both loci were identified as risk factors in the Northern Han Chinese population, and the A allele of rs13337493 [odds ratio (OR) 1.320, 95% confidence interval (CI) 1.052, 1.653, Pc = 0.036] and the T allele of rs9921222 (OR 1.351, 95% CI 1.045, 1.747, Pc = 0.042) showed increased susceptibility to PD. The risk effect of rs9921222 was predominant in the male cohort (OR 1.504, 95% CI 1.058, 2.139, Pc = 0.044). Rs13337493 was related to worse motor function in white individuals, which was represented by the Hoehn & Yahr stage (OR 2.775, 95% CI 1.195, 6.447, Pc = 0.036). It also correlated with compensatory elevation of cerebrospinal fluid (CSF) 3,4-dihydroxyphenylalanine (DOPA, β = 0.040, 95% CI 0.007, 0.073, Pc = 0.038).

Conclusion

Our findings support a gatekeeper role for AXIN1; its polymorphisms contribute to increased PD susceptibility and accelerated motor progression, yet may also trigger a compensatory presynaptic response, as evidenced by elevated CSF DOPA levels, to counteract neurodegeneration. Future studies should include larger sample sizes, more diverse ethnic populations, and protein-level investigations.