Document Type : Original Article
Authors
1
Endocrinology and Metabolism Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
2
Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
3
Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
10.30476/tips.2026.111205.1354
Abstract
Background: Childhood obesity has increased early-onset insulin resistance (IR), a key precursor to metabolic syndrome. The Wnt/β-catenin pathway regulates glucose homeostasis via the LRP6 co-receptor. While severe LRP6 mutations cause metabolic dysfunction, the common rs2302685 (V1062I) variant’s role in pediatric IR is unknown.
Methods: This cross-sectional study included 234 healthy children and adolescents (aged 9–18 years) from southern Iran. Genotyping of LRP6 rs2302685 was performed using PCR-RFLP. Seven surrogate indices of insulin sensitivity/resistance (HOMA-IR, QUICKI, insulin-to-glucose ratio, McAuley, revised McAuley, FIRI, Bennett’s index) were assessed. Multivariate logistic regression adjusted for age, sex, BMI, and Tanner stage.
Results: Genotype frequencies were 73.1% (TT), 25.6% (CT), and 1.3% (CC), in Hardy-Weinberg equilibrium. Univariate analysis showed no significant differences in biochemical or insulin indices across genotypes. Multivariate regression under dominant and recessive models confirmed that rs2302685 was not independently associated with any of the seven indices (all P > 0.05), even after adjusting for adiposity and puberty.
Conclusion: This comprehensive multi-index analysis demonstrates that LRP6 rs2302685 (V1062I) is not an independent genetic driver of early-onset insulin resistance in healthy Iranian children and adolescents. Despite prior links to dyslipidemia, its direct role in pediatric glucose homeostasis appears negligible. These findings help refocus future biomarker research on more relevant genetic targets for pediatric metabolic syndrome.
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