Delving the vitamin D receptor variation and expression profiles in the context of type 2 diabetes among families.

Background: Vitamin D is essential for insulin secretion and sensitivity. Consequently, its inadequacy is linked to higher insulin resistance and Type 2 Diabetes (T2D). The Vitamin D receptor (VDR) gene is one potential candidate for T2D, and multiple polymorphisms in VDR have been examined in various populations, but no conclusive answers have been provided.

Objectives: This study was designed to evaluate the susceptibility of VDR gene polymorphism and its expression in diabetic families in Pakistan.

Methodology: In this family-based study, twenty diabetic families with a positive family history of T2D and at least three T2D patients were recruited from outpatient clinics and public hospitals. The current study comprised 143 individuals with 55 affected and 88 unaffected individuals. Blood samples of the selected families were collected. DNA was extracted from the collected samples and the PCR-RFLP method was followed to identify the genotyping and RT-qPCR for expression. Phenotypic and genotypic pedigrees of the families were developed by the progeny online tool. The association values of SNPs were determined by TDT and DFAM analysis implemented on Plink software.

Results: The results explained a significant familial aggregation among phenotypic characters including Age, Gender, BMI (body mass index), age of disease diagnosis, disease duration, and blood pressure in the probands, affected FDRs (First Degree Relatives) and affected SDRs (Second Degree Relatives). A significant association of rs731236 C/T (OR = 1.522), rs2228570 C/T (OR = 1.327) with p < 0.05. Whereas, for rs1544410 G/A (OR = 0.9706) and rs7975232 T/G (OR = 0.7368) no considerable association evidence was seen (p > 0.05) in families. The mRNA expression of VDR increased threefold (p = 0.0204) in patients compared to controls. Variation-based expression analysis exhibited that the rs2228570 genotype influences the expression.

Conclusion: A linkage was found among the FDRs with probands. Variation in the gene VDR at loci rs731236 and rs2228570 was associated with familial T2D. However further research is required to explore more genetic factors that could influence T2D risks in families.