Relationship between polymorphisms in vitamin D metabolism-related genes and the risk of rickets in Han Chinese children.
BACKGROUND
Vitamin D deficiency rickets is common in China. Genetic factors may play an important role in the susceptibility to rickets. Our study aimed to identify the relationship between three vitamin D-related genes (group specific component [GC], cytochrome P450, family 2, subfamily R, polypeptide 1 (CYP2R1), and 7-dehydrocholesterol reductase/nicotinamide-adenine dinucleotide synthetase 1 (DHCR7/NADSYN1) and rickets in Han Chinese children from northeastern China.


METHODS
A total of 506 Han children from northeastern China were enrolled in the current study. Twelve SNPs in three candidate genes were genotyped using the SNaPshot assay. Linear regression was used to examine the effect of 12 single-nucleotide polymorphisms (SNPs) on the risk of rickets.


RESULTS
In our case-control cohort, six alleles of the 12 SNPs conferred a significantly increased risk of rickets in GC (rs4588 C, P = 0.003, OR: 0.583, 95% CI: 0.412-0.836; rs222020 C, P = 0.009, OR: 1.526, 95% CI: 1.117-2.0985; rs2282679 A, P = 0.010, OR: 0.636, 95% CI: 0.449-0.900; and rs2298849 C, P = 0.001, OR: 1.709, 95% CI: 1.250-2.338) and in CYP2R1 (rs10741657 G, P = 0.019, OR: 1.467, 95% CI: 1.070-2.011; and rs2060793 G, P = 0.023, OR: 0.689, 95% CI: 0.502-0.944). The results remained significant after adjustment for sex and body mass index. We further analyzed the effect of genotypes under three different genetic models. After using Bonferroni's method for multiple corrections, rs4588, rs2282679, and rs2298849 of the GC gene were significantly associated with rickets under the dominant (P =0.003 for rs4588, P =0.024 for rs2282679, and P =0.005 for rs2298849) and additive models (P = 0.006 for rs4588, P = 0.024 for rs2282679, and P = 0.005 for rs2298849). Haplotype analysis showed that the CAT haplotype of the GC gene (P = 0.005) and the GAA haplotype of the CYP2R1 gene (P = 0.026) were associated with susceptibility to rickets.


CONCLUSIONS
This case-control study confirmed the strong effect of GC and CYP2R1 loci on rickets in Han children from northeastern China.
Department of Pediatrics, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China. renlihong1@163.com.
Yuling
Y
Zhang
Shufen
S
Yang
Ye
Y
Liu
Lihong
L
Ren
D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002681:China; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics*; D015331:Cohort Studies; D000072467:Cytochrome P450 Family 2; D004198:Disease Susceptibility; D005260:Female; D056426:Genetic Loci; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D016017:Odds Ratio; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012279:Rickets / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D014809:Vitamin D-Binding Protein / Q000235:genetics*
D014809:Vitamin D-Binding Protein; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase