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bioRxiv · 10.1101/2025.11.23.690038

Association between KCNC1 gene polymorphism and blood lipid levels in determining the efficacy of high-intensity interval training

Lai, j.·gong, l.·liu, y.·li, y.·nie, j.·zhou, d.
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Abstract

ObjectiveThe potassium voltage-gated channel subfamily C member 1 (KCNC1) gene plays a crucial role in both neural excitability and lipid metabolism. However, the impact of its genetic polymorphisms on individual blood lipid levels and the efficacy of exercise interventions remains unclear. This study aimed to investigate the association between KCNC1 single nucleotide polymorphisms (SNPs) and baseline blood lipid levels in young Han Chinese individuals, as well as the relationship between lipid profiles and sensitivity to high-intensity interval training (HIIT). This research provides theoretical support for developing personalised exercise prescriptions based on genetic background to improve lipid health. MethodsThis study recruited 245 healthy Han Chinese university students (114 males, 131 females) without regular exercise habits. Participants underwent a standardised 12-week HIIT intervention programme, conducted three times weekly. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured before and after the intervention. Genotyping of the KCNC1 gene SNP was performed using the Infinium CGA chip. PLINK software was employed to construct linear regression models (with age, sex, BMI, and baseline lipid levels as covariates) to analyse the association between genetic polymorphisms and changes ({Delta}) in lipid parameters. ResultsFollowing 12 weeks of HIIT, all participants demonstrated significant improvements in TC, HDL-C, LDL-C, and TG levels (P<0.01). Association analysis revealed: 1) At baseline, the rs757511 locus was significantly correlated with HDL-C levels in males ({beta} = -0.112, P = 0.0445), with individuals carrying the A allele exhibiting higher baseline HDL-C; 2) Regarding HIIT responsiveness, three loci exhibited significant sex-specific associations: the C allele at rs6083540 was significantly associated with improved TG levels in females ({beta} = 0.1564, P = 0.025); the A allele at rs61882396 was significantly associated with improved TG levels in females ({beta} = -0.129, P = 0.032); the C allele at rs12574348 was significantly associated with improved LDL-C levels in males ({beta} = 0.1608, P = 0.048). ConclusionThis study first demonstrates an association between KCNC1 gene polymorphisms (rs6083540, rs12574348, rs61882396) and lipid sensitivity to HIIT in young Han Chinese populations, with this association exhibiting significant sex specificity. The findings suggest that the KCNC1 gene may serve as a key genetic mediator in exercise-regulated lipid metabolism. Future development of tailored HIIT programmes should account for individual genotypic and gender variations.

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Lai, j., gong, l., liu, y., li, y., nie, j., zhou, d.. 2025-11-26. Association between KCNC1 gene polymorphism and blood lipid levels in determining the efficacy of high-intensity interval training. https://doi.org/10.1101/2025.11.23.690038

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