青少年特发性脊柱侧弯患儿褪黑素受体1B基因多态性研究

目的 研究褪黑素受体1B(melatonin receptor 1B, MTNR1B)基因启动子区域多态性与青少年特发性脊柱侧弯(adolescent idiopathic scoliosis, AIS)发生发展的关系.方法 本研究包括814例AIS患儿及651例正常对照,所有AIS患儿最大cobb角大于20°.采用PCR-RFLP的方法 对所选取多态性位点(rs4753426、rs7941837)进行基因分型.结果 AIS患儿组rs4753426多态性位点基因型分布为TT 6.5%、TC 41.5%、CC 52.0%,正常对照组为TT 9.5%、TC 44.4%、CC 46.1%.AIS患儿组rs4753426多态性位点等位基因分布为T 27.3%、C 73.7%,正常对照组为T 31.7%、C 68.3%.AIS患儿组与正常对照相比,rs4753426多态性位点基因型分布及等位基因分布差异都有统计学意义(P值分别为0.025,0.009).AIS患儿组rs7941837多态性位点基因型分布为AA 21.2%、AT 50.2%、TT 28.6%,正常对照组为AA 17.6%、AT 50.6%、TT 31.7%.AIS患儿组rs7941837多态性位点等位基因分布为A 46.3%、T 53.7%,正常对照组为A 43.0%、T 57.0%.AIS患儿组与正常对照相比,rs7941837多态性位点基因型分布及等位基因分布差异都无统计学意义(P＞0.05).在已经达到骨骼成熟或者已经接受手术治疗的患儿组,MTNR1B基因启动子区2个多态性位点不同基因型所对应的平均最大Cobb角差异都没有统计学意义(P＞0.05).结论 MTNR1B基因启动子区域多态性位点rs4753426与AIS的发病相关,MTNR1B基因是AIS的一个易感基因,但它可能不是AIS的修饰基因.

The promoter polymorphisms of melatonin receptor 1B gene in adolescent idiopathic scoliosis

Objective To determine whether the promoter polymorphisms of melatonin receptor 1B gene (MTNR1B) associated with the predisposition and/or disease severity of adolescent idiopathic scoliosis (AIS). Methods Eight hundred and fourteen AIS patients and 651 normal controls were recruited in this study. The maximum Cobb angles of AIS patients were larger than 20 degrees. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)was performed to genotype two genetic variations (rs4753426、rs7941837) located in the MTNR1B promotor gene.ResultsFor rs4753426, the genotype frequencies were TT 6.5%, TC 41.5%, CC 52.0% in AIS patients, and TT 9.5%, TC 44.4%, CC 46.1% in controls; the allele frequencies were T 27.3%, C 73.7% in AIS patients and T 31.7%, C 68.3% in controls. The frequencies of genotype and allele of the rs4753426 were significantly different between AIS patients and controls (P=0.025, P=0.007, respectively). For rs7941837, the genotype frequencies were AA 21.2%, AT 50.2%, TT 28.6% in AIS patients, and AA 17.6%, AT 50.6%, TT 31.7% in controls; the allele frequencies were A 46.3%, T 53.7% in AIS patients, and A 43.0%, T 57.0% in controls. For rs7941837, both the frequencies of genotype and allele were not significant different between AIS patients and controls (P＞0.05). In the AIS patients who reached skeletal maturity or underwent corrective surgery, there was no difference in the mean maximum Cobb angles between the 2 variations of MTNR1B polymorphism.Conclusions Polymorphism of rs4753426 in the MTNR1B promoter gene is associated with the occurrence of AIS, suggesting MTNR1B is a predisposition gene rather than a modifying gene of AIS.