Title : Impact of SOST (Sclerostin) and LRP5 (low-density lipoprotein receptor-related protein- 5) genotype variant in early onset type 2 diabetes mellitus among young Indians
Abstract:
Objectives:
Type 2 diabetes mellitus (T2DM) presents a significant global health challenge, with rising prevalence rates. T2DM pathogenesis , particularly in early onset cases, is complex. Wnt signaling pathway plays a crucial role in islet cell development. Hence 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 young population of Uttarakhand, which is novel given that no studies have focused on this link within an Indian demographic.
Material and Method:
In This case control study T2DM patients between 20 and 40 years attended Medicine OPD were recruited as cases. After taking informed consent 5 ml blood was collected. Serum was used for lipid profile by enzymatic method and sclerostin by ELISA method. DNA isolated from EDTA blood was subjected to PCR-RFLP for restriction digestion by NCoI and HinfI enzymes. Statistical analysis was done by SPSS 23v. Comparison of genotypic variants was done by Chi2 test.
Results:
In this study of 114 early-onset T2DM cases and 115 sex-matched controls, genotype distributions of SOST rs865429 and LRP5 rs11228303 followed Hardy–Weinberg equilibrium. In cases, the SOST GG genotype showed a nonsignificant higher odds ratio (OR=2.0357) for T2DM, and was associated with higher 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, iPTH, and sclerostin levels. These findings indicate potential interactions between SOST and LRP5 variants and metabolic markers in early onsetT2DM.
Discussion/Conclusion:
The trend of elevated biochemical parameters in GG and TT genotype 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, multi-centric studies are neded to confirm the preliminary results.
