Association of SNPs in carbohydrate metabolism genes with insulin resistance indicators in the Mexican population.

Introduction: Insulin resistance (IR) is a key feature in the pathophysiology of metabolic disorders such as type 2 diabetes mellitus (T2DM) and obesity, both of which have a high prevalence in the Mexican population. Genetic predisposition plays a critical role in the development of IR, particularly through variants in carbohydrate metabolism genes. However, the specific contributions of these genetic factors in young Mexicans remain poorly characterized.

Objectives: This study aimed to identify associations between single nucleotide polymorphisms (SNPs) in carbohydrate metabolism-related genes and insulin resistance markers in a young Mexican population. Additionally, we sought to identify novel genetic variants that may contribute to metabolic risk and explore sex-specific genetic effects.

Methods: A genome-wide association study was conducted on 455 urban college students from Mexico. A total of 430 SNPs related to carbohydrate metabolism were genotyped. Clinical markers of IR, including fasting glucose, insulin, the homeostasis model assessment for insulin resistance (HOMA-IR), body mass index (BMI), body fat percentage (BF%), and waist circumference (WC), were evaluated. Associations between SNPs and metabolic traits were analyzed using logistic regression models adjusted for relevant covariates. Bonferroni correction was applied to account for multiple testing.

Results: Several SNPs were significantly associated with IR-related traits. SNPs in glucose metabolism genes, including GCK (rs1799884), SLC2 A9 (rs1122141), and IDH3B (rs6037255), were linked to fasting glucose levels, with IDH3B showing the strongest effect (OR 12.17, p = 0.0144). Variants in insulin-related genes, such as SLC2 A9, PFKP (rs3814591), and SLC45 A1 (rs12132135), were associated with elevated insulin and HOMA-IR. Adiposity-related SNPs, including those in PDK3 (rs7889665), PGK1 (rs2076630), and IDH2 (rs62019177), influenced body fat percentage and BMI. Notably, the novel variant rs77487659 (PGLS) was significantly associated with IR, particularly in women (OR 5.5, p = 0.00005), highlighting a potential sex-specific effect. The SLC45 A1 variant rs12132135 demonstrated significant associations with multiple metabolic traits, including BMI, WC, and insulin resistance.

Conclusion: This study provides a comprehensive genetic analysis of IR-related traits in young Mexicans, highlighting both previously reported and novel associations. The findings suggest that genetic predisposition plays an important role in metabolic risk, with potential implications for early screening and personalized interventions. Sex-specific effects emphasize the need for tailored approaches in genetic risk assessment. Future research should focus on functional validation of these SNPs and their integration into precision medicine strategies for metabolic disease prevention.