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

Abstract

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 (SOST) and low-density lipoprotein receptor-related protein-5 (LRP5) 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 (SOST) rs865429 and LRP5 rs11228303 followed Hardy-Weinberg equilibrium. In cases, the SOST 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 LRP5 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 SOST 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 SOST and LRP5 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 SOST and LRP5 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.