Association of VDR haplotypes with vitamin D status: a comparative pilot study identifying the F−t combination as a risk factor in South India

Introduction Vitamin D receptor ( VDR ) gene polymorphisms are key genetic determinants of vitamin D status. This pilot study investigated the association of FokI and TaqI polymorphisms with serum vitamin D levels in a South Indian cohort from Mysore. Methods 60 participants were categorised into vitamin D deficient (<20 ng/mL, n=30) and insufficient (21–29 ng/mL, n=30) groups. Genotyping was performed and allele frequencies were compared with 12 regional and 02 global studies. Haplotype frequencies were estimated using the Expectation-Maximisation algorithm. Results The mean age was significantly lower in the deficient group (28.43±12.97 years) compared with the insufficient group (42.87±15.88 years; p=0.004). While single-nucleotide polymorphism (SNP) analysis showed no significant association with vitamin D levels (p>0.05), haplotype analysis revealed a highly significant difference between groups (p<0.001). The F−t haplotype (Wild FokI –Mutant TaqI ) was enriched in the deficient group (36.7%) compared with the insufficient group (15.5%). Comparative analysis showed that the TaqI ‘t’ allele frequency (33%) of the present cohort significantly diverged from East Asian populations (7%, p<0.001) but aligned with Mediterranean profiles. Conclusions This pilot study of 60 participants could not detect individual SNP associations, while the F−t haplotype was found to be associated with severity of deficiency within low vitamin D individuals. These findings suggest that younger, non-diabetic adults in South India carry a unique genetic predisposition, highlighting the necessity of haplotype-based screening in South Indian clinical practice.