Genetic insights into vitamin D deficiency: a case-control study of GC and CYP24A1 gene polymorphism

• Published in: Steroids Vol. 218; p. 109607
• Main Authors: Usama, Khan, Aslam, Raza, Muhammad Kashif, Abbas, Khurram, Mansour, Lamjed, Ali, Aktar, Imran, Muhammad
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2025
• Subjects: Adult; Case-Control Studies; CYP24A1; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide - genetics; Single nucleotide polymorphism; Vitamin D - blood; Vitamin D binding protein; Vitamin D deficiency; Vitamin D Deficiency - blood; Vitamin D Deficiency - genetics; Vitamin D-Binding Protein - genetics; Vitamin D3 24-Hydroxylase - genetics; Vitamin D deficiency; Vitamin D binding protein; CYP24A1; Single nucleotide polymorphism
• ISSN: 0039-128X; 1878-5867; 1878-5867
• DOI: 10.1016/j.steroids.2025.109607

Population size, Biochemical Profile, Genotype of DBP & CYP24A1 alleles and its association with risk of vitamin D deficiency. [Display omitted] •This study investigates the impact of SNPs in GC and CYP24A1 genes on vitamin D deficiency.•The G/T genotype of D432E and A/A genotype of T436K in the GC gene are linked to an increased risk of vitamin D deficiency.•Polymorphisms in CYP24A1 (rs4809960 and rs2585428) are significantly associated with a higher risk of vitamin D deficiency.•The D432E and T436K variants in the GC gene correlate with lower vitamin D levels and elevated PTH in deficient individuals.•A negative correlation between serum 25-hydroxyvitamin D and PTH levels underscores their regulatory relationship. Despite the sunny climate, vitamin D deficiency is highly prevalent in several parts of the world. Several risk factors are associated with VD deficiency, including single nucleotide polymorphism and post-translational modifications in its transport protein, known as vitamin D binding protein (DBP) or GC and CYP24A1, a protein associated with its degradation. Our study explores the impact of rs4588 and rs7041 in the GC gene, along with CYP24A1 rs4809960 and rs2585428, on serum vitamin D and the risk of vitamin D insufficiency. This study enrolled 114 healthy controls and 239 vitamin D-deficient subjects. SNPs were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The G/T genotype of D432E and the A/A genotype of T436K in the GC gene were observed to be risk factors for vitamin D deficiency. Overall, a significant (P < 0.05) association was observed between the D432E and T436K polymorphism and vitamin D deficiency. Polymorphic genotypes of CYP24A1 rs4809960 and rs2585428 polymorphisms were significantly associated with a higher risk of Vitamin D deficiency. D432E and T436K polymorphisms were associated with decreased vitamin D and increased PTH levels in vitamin D-deficient individuals. Similarly, both CYP24A1 polymorphisms were significantly associated with a higher risk of vitamin D deficiency. Also, a negative association was observed between sufficient serum levels of 25-hydroxyvitamin D and PTH levels.