目的：COL9A1 基因是位于单纯性马蹄内翻足（ICTEV）易感区域(6q12-13)的已知基因。本研究探讨 COL9A1 基因在 ICTEV 患者中的表达及其单核苷酸多态 (SNP) 位点在ICTEV 和正常人中的分布情况。方法：应用免疫组化方法检测 25 例 ICTEV 患儿及 5 例正常对照组肌肉及肌腱组织中 COL9A1 的表达；应用限制性片段长度多态性技术结合测序法，分析 118 例 ICTEV 患者及 100 名正常人 COL9A1 基因的 2 个 SNP位点基因型。结果：88%（22/25）的 ICTEV 患者 COL9A1蛋白表达阳性，明显高于正常对照组。位于 COL9A1 基因编码区的 SNP 位点 rs1135056 的基因型频率和等位基因频率在两组人群中的分布差异有统计学意义（P<0.05）：ICTEV 组 G 等位基因频率高于对照组；与对照组相比，AA 基因型频率降低，AG、GG 基因型频率增高。结论：COL9A1 基因在 ICTEV 中高表达，rs1135056多态位点G等位基因和ICTEV的发生相关。
Abstract
OBJECTIVE: COL9A1 gene is located in the susceptibility region of idiopathic congenital talipes equinovarus (ICTEV) (6q12-13). This study aimed to investigate the expression of the COL9A1 gene and the distribution of single nucleotide polymorphism (SNP) of COL9A1 gene in patients with ICTEV and normal controls. METHODS: Immunohistochemistry was used to detect the expression of COL9A1 in 25 children with ICTEV and 5 normal controls. The frequencies of genotypes and allele of two SNPs in COL9A1 gene rs35470562 and rs1135056 were investigated by PCR-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing in 118 patients with ICTEV and 100 normal controls. RESULTS: The COL9A1 protein expression was significantly higher in 22 (88%) out of 25 children with ICTEV than normal controls. There were significant differences in the frequencies of genotypes and allele of rs1135056 in COL9A1 gene between the ICTEV and the control groups: the G allele frequency was higher, the frequency of AA genotype was lower, and the frequencies of AG and GG genotypes were higher in ICTEV patients than those in healthy controls (P<0.05). CONCLUSIONS: COL9A1 protein is highly expressed in patients with ICTEV and rs1135056, which is located in the coding region of COL9A1 gene, may be associated with the pathogenesis of ICTEV.
关键词
单纯性马蹄内翻足 /
COL9A1基因 /
单核苷酸多态 /
儿童
Key words
Idiopathic congenital talipes equinovarus /
COL9A1 gene /
Single nucleotide polymorphism /
Child
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