Molecular Study of SP1 Binding Site of COL1A1 Gene in Children Affected with Vitamin D Deficiency Rickets

Abstract Background Rickets is a disease associated with delayed bone growth in infants and children due to impaired mineralization and ossification of the growth plates. The main cause of rickets is Vitamin D deficiency. Collagen type I is one of the key proteins involved in the maturation, development and mineralization of bone. Objective To investigate the possible association between occurrence and severity of vitamin D deficiency rickets and the allelic polymorphisms within COL1A1 Sp1 binding site gene. Patients and Methods This case-control study included 30 cases with active vitamin D deficiency rickets aged (6-36) months as well 30 healthy controls with matching age and sex. All subjects in the study were subjected to complete history taking with complete clinical examination and investigated for serum calcium, phosphorus, alkaline phosphatase (ALP), X-rays of distal ends of long bones (radius, ulna, tibia and femur), X- ray chest and genetic analysis for Sp1 binding site polymorphisms within Collagen 1 Alpha 1 (COL1A1) gene of type 1 collagen genotyped by Polymerase Chain Reaction (PCR)-RFLP method. Results The study subjects were 30 cases, 16 (53.3%) males and 14 (46.7%) females, and 30 controls, 15 (50.0%) males and 15 (50.0%) females, with matched age and sex. All signs of rickets were evident in cases than controls with p-value <0.001. According to laboratory data, there was no significant difference between cases and controls regarding calcium levels 8.80 ± 0.99 versus 9.24 ± 0.73 mg/dl respectively, while there was significant decrease in the level of phosphorus and increase in the level of ALP in cases than controls, phosphorus 3.50 ± 0.73 versus 4.99 ± 0.53 mg/dl and ALP 641.80 ± 283.86 versus 142.13 ± 54.30 U/L, respectively. Regarding molecular genetics, dominant homozygous type (SS) was higher among controls 73.3% while dominant heterozygous type (Ss) was higher among cases 56.7% with p-value = 0.004 and 0.008; respectively. Also there was no significant difference between controls and cases regarding the percentage of recessive homozygous type (ss) with p-value = 0.554. The comparison between the two groups regarding allele distribution showed higher percentage of (s) allele in cases than controls 35.0% versus 15.0%; respectively with p-value = 0.011. Conclusion Our study found that Genetic polymorphisms of SP1 binding site of Collagen 1 Alpha1 (COL1A1) gene are associated with vitamin D deficiency rickets, low bone mineral density and higher risk of fractures in children. The study highlights the importance of genetic factors in the development of rickets in infants and children and suggests that COL1A1 gene polymorphisms may serve as a potential genetic marker for identifying children at-risk.