Vitamin D deficiency rickets often causes growth retardation, impaired bone formation and hypocalcemia in children. It is well known that rickets is mainly caused by vitamin D deficiency, but whether there is hereditary susceptibility of children to develop vitamin D deficiency rickets is unknown. Vitamin D receptor (VDR) gene has been used as one of genetic markers in studying the metabolic diseases of bone. The present study aimed to explore the hereditary susceptibility of children to develop rickets through studying the association between VDR gene start codon polymorphism and vitamin D deficiency rickets,The subjects were selected from Kunming city, every subject was of Han ethnic group. The subjects were composed of two groups, the patient group consisted of 48 children with active vitamin D deficiency rickets which was diagnosed clinically and confirmed radiologically; the control group was composed of 92 normal children. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), DNA sequence analysis and genetic analysis methods were used. A restriction fragment length polymorphism in the start codon of VDR gene (FokI) was tested in both groups.VDR gene start codon polymorphism was tested successfully for every subject. Frequencies of FF, Ff and ff genotypes were 46%, 33% and 21% in the rickets group, and 22%, 52% and 26% in the control group, respectively. A significant difference was found in the frequency distribution of VDR genotype between two groups (chi(2) = 8.912, P = 0.012). In the patient group, Ff and ff genotypes were less common than control group, but the FF genotype was more common than control group (OR = 3.046), indicating that FF genotype may be significantly associated with vitamin D deficiency rickets. Moreover, VDR allele frequencies of FokI polymorphism also showed significant difference between the two groups (chi(2) = 5.451, P = 0.020), F alleles were more common in patient group than in control group. DNA sequence analysis identified that the start codon of F allele was mutated from ATG to ACG.There is an association between VDR gene start codon polymorphism and vitamin D deficiency rickets. This study suggested the possibility that VDR gene polymorphism might be important in determining an individual's susceptibility to development of vitamin D deficiency rickets.