Dyslipidemia frequently occurs alongside type 2 diabetes mellitus (T2DM) and increases the risk of atherosclerosis. VPS26A rs1802295 (C > T) is a susceptibility locus for T2DM identified in a genome-wide association study among South Asians, but its connection with lipid traits in North Indians remains unclear. 

This study aims to examine the association between rs1802295 genotypes and lipid profile abnormalities.

This observational case-control study was carried out at King George’s Medical University in India from November 2024 to November 2025, and enrolled 50 T2DM cases and 30 BMI- and ethnicity-matched normoglycemic controls according to the American Diabetes Association criteria: glycated hemoglobin (HbA1c) ≥ 6.5% (48 mmol/mol) and fasting plasma glucose ≥ 126 mg/dL (7.0 mmol/L). Following written informed consent, fasting blood samples were used for glucose/HbA1c and serum lipid profiling, and genomic DNA was extracted to genotype VPS26A rs1802295 (C > T) by PCR followed by Sanger sequencing. Group comparisons used t-tests, and genotype-lipid associations were evaluated with one-way ANOVA; genotype/allele distributions, Hardy-Weinberg equilibrium, and odds ratios were assessed using chi-square tests in SPSS (p < 0.05).

T2DM participants exhibited significantly higher levels of total cholesterol (TC), triglycerides (TG), very low-density lipoprotein (VLDL), and the LDL/HDL ratio (all p-values < 0.05). Within the T2DM group, TC showed a significant association with rs1802295 genotypes (p = 0.045), with the TT genotype having the highest mean TC (154.75 ± 57.39 mg/dL) compared to CC (109.79 ± 30.40 mg/dL) and CT (114.74 ± 48.26 mg/dL). The LDL/HDL ratio also significantly differed among genotypes in cases (p = 0.011). However, the distribution of rs1802295 genotypes was not significantly linked to T2DM risk.

In this pilot North Indian cohort, T2DM participants showed a dyslipidemic pattern consistent with previous Indian and global literature. More importantly, VPS26A rs1802295 showed genotype-wise differences in lipid parameters among individuals with T2DM, particularly for total cholesterol and LDL/HDL ratio, suggesting a possible role of this variant in lipid dysregulation. However, rs1802295 was not significantly associated with T2DM risk this cohort, despite genome-wide association studies (GWAS) identifying it as a T2DM susceptibility marker. Larger sex-balanced and multi-center studies are required to confirm whether VPS26A rs1802295 may act as a genetic modifier of diabetic dyslipidemia.