Potential genetic markers predicting the outcome of brace treatment in patients with adolescent idiopathic scoliosis
Potential genetic markers predicting the outcome of brace treatment in patients with adolescent idiopathic scoliosis
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DOI：
10.1007/s00586-011-1874-7
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发表时间：
2011-10-01
影响因子：
2.8
通讯作者：
Qiu, Yong
中科院分区：
文献类型：
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作者：
Xu, Leilei;Qiu, Xusheng;Qiu, Yong
为了研究先前报道的与青少年特发性脊柱侧凸(AIS)的发生或脊柱侧弯严重程度相关的易感基因是否在支具治疗的效果中起作用。在支具治疗开始和每次随访时记录主弯的Cobb角。根据支具治疗结果(成功/失败)将患者分为两组。支架治疗失败的定义是，与最初的Cobb角或手术干预相比，由于弯曲进展，弯曲进展超过5A度。选择雌激素受体α(ERα)、雌激素受体β(ERβ)、色氨酸羟化酶1(TPH-1)、褪黑素受体1B(MTNR1B)和Matrlin-1(MATN1)基因的单核苷酸多态(SNP)位点，采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法进行基因分型。用卡方检验比较两组间的基因型和等位基因分布差异。用Logistic回归分析找出支具治疗结果的独立预测因素，失败组90例(28.8%)，成功组222例(71.2%)。在失败组中，ERα基因rs9340799单核苷酸与GA(50.9vs.17.9%p<；0.001)和G等位基因(27.1vs.12.0%，p<；0.001)相关。TPH-1基因rs10488682位点的AT等位基因(33.3vs.13.0%，p=0.002)和A等位基因(16.7vs.9.6%，p=0.033)也与此相关。MTNR1B基因在两组间的基因分布差异有统计学意义，等位基因分布在两组间差异有统计学意义，而在MATN1和ERβ基因上，两组间的基因或等位基因分布差异无统计学意义。Logistic回归分析显示ERα和TPH-1是预测支具疗效的独立因素，ERα和TPH-1可能是预测支具治疗效果的潜在遗传标志物。ERα基因rs9340799位G等位基因和TPH-1基因rs10488682位A等位基因的患者对支架治疗耐药。
To investigate whether the predisposition genes previously reported to be associated with the occurrence or curve severity of adolescent idiopathic scoliosis (AIS) play a role in the effectiveness of brace treatment.A total of 312 AIS patients treated with bracing were enrolled in this study. The Cobb angle of the main curve was recorded at the beginning of brace treatment as well as at each follow-up. The patients were divided into two groups according to the outcome of brace treatment (success/failure). The failure of brace treatment was defined as a curve progression of more than 5A degrees compared to the initial Cobb angle or surgical intervention because of curve progression. Single nucleotide polymorphism (SNP) sites in the genes for estrogen receptor alpha (ER alpha), estrogen receptor beta (ER beta), tryptophan hydroxylase 1 (TPH-1), melatonin receptor 1B (MTNR1B) and matrillin-1 (MATN1), which were previously identified to be predisposition genes for AIS, were selected for genotyping by the PCR-RFLP method. Differences of genotype and allele distribution between the two groups were compared by the chi(2) test. A logistic regression analysis was used to figure out the independent predictors of the outcome of brace treatment.There were 90 cases (28.8%) in the failure group and 222 cases (71.2%) in the success group. Patients in the failure group were associated with the genotype GA (50.9 vs. 17.9% p < 0.001) and the G allele (27.1 vs. 12.0%, p < 0.001) at SNP rs9340799 of the ER alpha gene. Similarly, they were also associated with the genotype AT (33.3 vs. 13.0%, p = 0.002) and the A allele (16.7 vs. 9.6%, p = 0.033) at SNP rs10488682 of the TPH-1 gene. For MTNR1B, the difference of genotype distribution between the two groups was found to be statistically significant, while the difference of allele distribution between the two groups was found to be marginally statistically significant; for the MATN1 and ER beta genes, we found no significant differences of the genotype or allele distribution between the two groups. In the logistic regression analysis, ER alpha and TPH-1 were demonstrated to be independent factors predictive of bracing effectiveness.ER alpha and TPH-1 might be potential genetic markers that could predict the outcome of brace treatment. Patients with the G allele at the rs9340799 site of the ER alpha gene and the A allele at the rs10488682 site of the TPH-1 gene are prone to be resistant to brace treatment.