Interaction Analysis of VDR rs7975232 Polymorphism and the Triglyceride-Glucose Index in Relation to Metabolic Outcomes in Older Adults

Ageing is associated with increasing metabolic heterogeneity driven by interactions between adipose tissue dysfunction and altered glucose-lipid metabolism. The vitamin D receptor (VDR) rs7975232 polymorphism has been investigated in relation to metabolic traits; however, its relationship with glucose–lipid metabolic characteristics remains unclear. This study aimed to investigate the association of the VDR rs7975232 polymorphism with metabolic markers and whether their relationships with the TyG index differ according to genotype in older adults. The study included 95 older adults living in a long-term care facility (mean age 62.71 ± 14.13 years). Anthropometric and fasting biochemical parameters were assessed, and the triglyceride–glucose (TyG) index, homeostatic model assessment of insulin resistance (HOMA-IR), and atherogenic index of plasma (AIP) were calculated. VDR rs7975232 genotyping was performed using real-time PCR. Multivariable linear regression models assessed genotype × TyG interactions after adjustment for age, sex, and waist-to-hip ratio. The rs7975232 genotype was not independently associated with TyG, NEFA, AIP, or other metabolic characteristics. In multivariable models using continuous TyG, genotype × TyG interactions were not statistically significant for NEFA or AIP. A nominal interaction was observed for fasting glucose, whereas no significant interactions were observed for log-transformed fasting insulin or log-transformed HOMA-IR. None of the genotype × TyG interactions remained statistically significant after Benjamini–Hochberg false-discovery-rate correction. In the exploratory categorical sensitivity analysis, AA genotype × higher TyG category interactions had nominal p-values < 0.05 for NEFA and AIP. In this exploratory cross-sectional cohort, VDR rs7975232 was not independently associated with the assessed metabolic traits. The primary analyses did not provide robust evidence of genotype-dependent differences in TyG–metabolic associations. Nevertheless, exploratory analysis using categorized TyG suggested potential genotype-dependent differences in associations with NEFA and AIP. These findings are hypothesis-generating and require confirmation in larger independent cohorts.