Genetic Insights Into Early-Onset Type 2 Diabetes Mellitus: The Role of SOST and LRP5 Genotypic Variants in Young Indians

Background Type 2 diabetes mellitus (T2DM) presents a significant global health challenge, with increasing prevalence rates. The pathogenesis of early-onset T2DM is complex, with the Wnt signaling pathway playing a crucial role in islet cell development. Purpose This study was designed to explore the association of sclerostin (<i>SOST</i>) and low-density lipoprotein receptor-related protein-5 (<i>LRP5</i>) gene polymorphisms with early-onset T2DM in the young population of Uttarakhand, which is novel given that no studies have focused on this link within an Indian demographic. Methodology In this case-control study, T2DM patients between 20 and 40 years old who attended Medicine OPD were recruited as cases. After taking informed consent, 5 mL of blood was collected. Serum was used for lipid profile using the enzymatic method and sclerostin using the enzyme-linked immunosorbent assay (ELISA) method. DNA isolated from whole blood was subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for restriction digestion by NCoI and HinfI enzymes. Statistical analysis was done using IBM SPSS Statistics for Windows, Version 23 (Released 2015; IBM Corp., Armonk, New York). A comparison of genotypic variants was made using a chi-square test. Results In this study of 114 early-onset T2DM cases and 115 sex-matched controls, genotype distributions of the gene that codes for the protein sclerostin (<i>SOST</i>) rs865429 and <i>LRP5</i> rs11228303 followed Hardy-Weinberg equilibrium. In cases, the <i>SOST</i> GG genotype showed a nonsignificant higher odds ratio (OR=2.035) for T2DM, and it was associated with higher low-density lipoprotein (LDL) levels (p=0.027), HbA1c, and triglycerides. The <i>LRP5</i> CT genotype in cases was linked to significantly higher HbA1c (p=0.018) and elevated triglycerides and calcium, while the TT genotype showed the highest levels across multiple clinical parameters. The <i>SOST</i> GG genotype also suggested a possible link with bone metabolism due to elevated calcium, intact parathyroid hormone (iPTH), and sclerostin levels. These findings indicate potential interactions between <i>SOST</i> and <i>LRP5</i> variants and metabolic markers in early-onset T2DM. Conclusion The trend of elevated biochemical parameters in GG and TT genotypes and higher odds ratio (OR=2.035) concludes that <i>SOST</i> and <i>LRP5</i> variants may contribute to early-onset T2DM and related complications. These findings highlight the importance of genetic predisposition in T2DM, pointing to a need for personalized clinical approaches. Larger, multicenter studies are needed to confirm these preliminary results.