维生素 D 代谢相关基因多态性与汉族儿童佝偻病发病风险的关系。
Relationship between polymorphisms in vitamin D metabolism-related genes and the risk of rickets in Han Chinese children.
机构信息
Department of Pediatrics, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
出版信息
BMC Med Genet. 2013 Sep 30;14:101. doi: 10.1186/1471-2350-14-101.
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.
背景
维生素 D 缺乏性佝偻病在中国很常见。遗传因素可能在佝偻病的易感性中起重要作用。我们的研究旨在确定三个与维生素 D 相关的基因（群体特异性成分[GC]、细胞色素 P450 家族 2 亚家族 R 多肽 1（CYP2R1）和 7-脱氢胆固醇还原酶/烟酰胺腺嘌呤二核苷酸合成酶 1（DHCR7/NADSYN1）与来自中国东北地区的汉族儿童佝偻病之间的关系。
方法
本研究共纳入 506 名来自中国东北地区的汉族儿童。使用 SNaPshot 测定法对三个候选基因中的 12 个 SNP 进行基因分型。线性回归用于检查 12 个单核苷酸多态性（SNP）对佝偻病风险的影响。
结果
在我们的病例对照队列中，GC 中六个等位基因的 12 个 SNP 显著增加了佝偻病的风险（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；和 rs2298849 C，P=0.001，OR：1.709，95%CI：1.250-2.338）和 CYP2R1（rs10741657 G，P=0.019，OR：1.467，95%CI：1.070-2.011；和 rs2060793 G，P=0.023，OR：0.689，95%CI：0.502-0.944）。在调整性别和体重指数后，结果仍然显著。我们进一步分析了三种不同遗传模型下基因型的作用。使用 Bonferroni 法进行多次校正后，GC 基因的 rs4588、rs2282679 和 rs2298849 与显性（rs4588 的 P=0.003，rs2282679 的 P=0.024，rs2298849 的 P=0.005）和加性模型（rs4588 的 P=0.006，rs2282679 的 P=0.024，rs2298849 的 P=0.005）显著相关。单倍型分析表明，GC 基因的 CAT 单倍型（P=0.005）和 CYP2R1 基因的 GAA 单倍型（P=0.026）与佝偻病易感性相关。
结论
这项病例对照研究证实了 GC 和 CYP2R1 基因座对中国东北地区汉族儿童佝偻病的强烈影响。
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