Yeung H Y, Tang N L, Lee K M, Ng B K W, Hung V W Y, Kwok R, Guo X, Qin L, Cheng J C Y
Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, China.
Stud Health Technol Inform. 2006;123:18-24.
IGF-I has a pivotal role in bone growth and could be one of the putative disease-modifier genes in AIS. Two SNPs in IGF-I gene promoter region were studied for any association with occurrence of AIS and for their effect on the curve severity among AIS.
506 AIS girls (Cobb>20 degrees) and 227 age-matched Chinese girls were recruited. The spine (L2-L4) and hip BMD of the subjects were measured by DXA. A subgroup of AIS patients (N=340) who were followed-up to skeletal maturity and the maximum Cobb's angle was recorded. Two SNPs were genotyped by PCR-RFLP (rs5742612 and rs2288377). The chi-square test and one-way ANOVA were used to test the association between genotypes and quantitative parameters, respectively.
No association was between the genotypes and the occurrence of AIS and the BMD of the spine and hip. The allelic frequency of T allele was 0.69 in AIS and control. However, the Cobb's angle was higher in patients with the homozygous T allele (Mean Cobb's angle: 38.1 degrees in TT vs 35.9 degrees in TC vs 33.2 degrees in CC group; p=0.04).
Interestingly, IGF-I polymorphism affects the curve severity of AIS though it was not associated with onset of AIS per se. It indicates that IGF-I may be a disease modifying gene. The importance of IGF-I in skeletal growth makes it a good candidate gene which would play a role in the documented association of rapid growth with curve progression in AIS.
胰岛素样生长因子-I（IGF-I）在骨骼生长中起关键作用，可能是特发性脊柱侧凸（AIS）中假定的疾病修饰基因之一。研究了IGF-I基因启动子区域的两个单核苷酸多态性（SNP）与AIS发生的相关性及其对AIS患者曲线严重程度的影响。
招募了506名AIS女孩（Cobb角>20度）和227名年龄匹配的中国女孩。通过双能X线吸收法（DXA）测量受试者的脊柱（L2-L4）和髋部骨密度。对一组随访至骨骼成熟的AIS患者（N=340）记录最大Cobb角。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对两个SNP进行基因分型（rs5742612和rs2288377）。分别采用卡方检验和单因素方差分析来检验基因型与定量参数之间的相关性。
基因型与AIS的发生以及脊柱和髋部的骨密度之间均无关联。AIS组和对照组中T等位基因的频率均为0.69。然而，纯合T等位基因的患者Cobb角更高（平均Cobb角：TT组为38.1度，TC组为35.9度，CC组为33.2度；p=0.04）。
有趣的是，IGF-I多态性虽与AIS本身的发病无关，但影响AIS的曲线严重程度。这表明IGF-I可能是一个疾病修饰基因。IGF-I在骨骼生长中的重要性使其成为一个很好的候选基因，可能在AIS中已记录的快速生长与曲线进展的关联中发挥作用。
