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Objectives <p>This study explored associations of folate metabolic gene polymorphisms and serum folate, vitamin B12, homocysteine with sudden total hearing loss, and analyzed their correlations with treatment response to screen potential prognostic markers. Methods: Serum folate, homocysteine, and vitamin B12 levels were measured in both groups. Genomic DNA was extracted, and genotypes of <i>MTHFR C677T/A1298C</i>, <i>MTR A2756G</i>, and <i>MTRR A66G</i> were determined by PCR.</p> Results <p>Serum folate was lower and vitamin B12 higher in the study group (<i>P</i> = 0.037, <i>P</i> = 0.047). Only <i>MTR A2756</i>G showed intergroup genotypic differences; <i>AG</i> + <i>GG</i> was more common in controls under the dominant model (<i>P</i> = 0.011, OR = 0.488, 95%CI: 0.278–0.857). <i>MTHFR 677TT</i> carriers had higher HCY than <i>CC</i> carriers (corrected P = 0.033). Folate level was negatively correlated with hearing loss severity (<i>P</i> &lt; 0.001). Pure-tone thresholds improved significantly after treatment (<i>P</i> &lt; 0.001), with variable recovery across individuals. Binary regression identified <i>MTR</i> genotype and folate as independent correlates of sudden total hearing loss. After adjustment, higher folate was an independent protective factor (<i>P</i> = 0.032, OR = 0.969, 95%CI: 0.941–0.997). <i>MTHFR 1298AC</i> (<i>P</i> = 0.036, OR = 76.439, 95%CI: 1.33–4391.47), <i>MTHFR 1298CC</i> (<i>P</i> = 0.022, OR = 6.66, 95%CI: 1.32–33.54) and <i>MTRR 66AG</i> (<i>P</i> = 0.008, OR = 12.01, 95%CI: 1.89–76.32) genotypes were independently associated with favorable hearing recovery.</p> Conclusion <p>Polymorphisms of <i>MTHFR A1298C</i> and <i>MTRR A66AG</i> were associated with better hearing recovery in patients with sudden total hearing loss after confounder adjustment. Higher serum folate was an independent protective correlate for sudden total hearing loss. Patients carrying <i>MTHFR 677TT</i> had elevated homocysteine, suggesting potential benefits of folate supplementation that need interventional verification. Serum folate could act as an auxiliary biomarker for disease risk and prognosis. Further prospective trials are required to confirm the therapeutic and preventive roles of folate supplementation.</p>

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Association of MTHFR (1298AC/CC), and MTRR (66AG) polymorphisms with treatment efficacy in sudden total hearing loss

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月9日

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  • Ting Xu,
  • Renbin Zhao,
  • Tao Lv,
  • Yang Huang

摘要

Objectives

This study explored associations of folate metabolic gene polymorphisms and serum folate, vitamin B12, homocysteine with sudden total hearing loss, and analyzed their correlations with treatment response to screen potential prognostic markers. Methods: Serum folate, homocysteine, and vitamin B12 levels were measured in both groups. Genomic DNA was extracted, and genotypes of MTHFR C677T/A1298C, MTR A2756G, and MTRR A66G were determined by PCR.

Results

Serum folate was lower and vitamin B12 higher in the study group (P = 0.037, P = 0.047). Only MTR A2756G showed intergroup genotypic differences; AG + GG was more common in controls under the dominant model (P = 0.011, OR = 0.488, 95%CI: 0.278–0.857). MTHFR 677TT carriers had higher HCY than CC carriers (corrected P = 0.033). Folate level was negatively correlated with hearing loss severity (P < 0.001). Pure-tone thresholds improved significantly after treatment (P < 0.001), with variable recovery across individuals. Binary regression identified MTR genotype and folate as independent correlates of sudden total hearing loss. After adjustment, higher folate was an independent protective factor (P = 0.032, OR = 0.969, 95%CI: 0.941–0.997). MTHFR 1298AC (P = 0.036, OR = 76.439, 95%CI: 1.33–4391.47), MTHFR 1298CC (P = 0.022, OR = 6.66, 95%CI: 1.32–33.54) and MTRR 66AG (P = 0.008, OR = 12.01, 95%CI: 1.89–76.32) genotypes were independently associated with favorable hearing recovery.

Conclusion

Polymorphisms of MTHFR A1298C and MTRR A66AG were associated with better hearing recovery in patients with sudden total hearing loss after confounder adjustment. Higher serum folate was an independent protective correlate for sudden total hearing loss. Patients carrying MTHFR 677TT had elevated homocysteine, suggesting potential benefits of folate supplementation that need interventional verification. Serum folate could act as an auxiliary biomarker for disease risk and prognosis. Further prospective trials are required to confirm the therapeutic and preventive roles of folate supplementation.