Association Study of BMP4, IL6, Leptin, MMP3, and MTNR1B Gene Promoter Polymorphisms and Adolescent Idiopathic Scoliosis
Association Study of BMP4, IL6, Leptin, MMP3, and MTNR1B Gene Promoter Polymorphisms and Adolescent Idiopathic Scoliosis
复制标题
DOI：
10.1097/brs.0b013e318a511b0e
复制
发表时间：
2011-01-15
期刊：
影响因子：
3
通讯作者：
Illes, Tamas
中科院分区：
文献类型：
--
作者：
Morocz, Monika;Czibula, Agnes;Illes, Tamas
学习设计。对来自独立匈牙利血统的 126 名青少年特发性脊柱侧凸患者和 197 名健康对照者进行了遗传关联研究。 目的。揭示骨形态发生蛋白 4 (BMP4)、白细胞介素 6 (IL6)、瘦素、基质金属蛋白酶 3 (MMP3)、褪黑激素 1B 受体 (MTNR1B) 基因启动子多态性在青少年特发性脊柱侧凸 (AIS) 中的意义。还研究了这些候选基因的组合关联，以检测某些单核苷酸多态性 (SNP) 模式的累加效应。背景数据摘要。之前的研究表明IL6、MMP3和MTNR1B基因可以被认为是AIS的易感基因。由于 BMP4 和瘦素在骨形成和重塑中发挥核心作用，并且与褪黑激素、IL6 和 MMP3 直接相互作用，因此这些也可能是潜在的易感基因。通过聚合酶链式反应-限制性片段长度多态性确定基因分型。结果。在单基因水平上，病例和对照之间这些基因多态性的等位基因和基因型频率没有发现显着差异；因此，之前检测到的 IL6、MMP3 和 MTNR1B 与 AIS 的关联并未通过独立 SNP 分析在匈牙利人群中得到证实。然而，在候选基因配对 SNP 的特定基因型组合中观察到 AIS 风险显着增加。结论。 BMP4、IL6、瘦素、MMP3 和 MTNR1B 启动子多态性的遗传效应可对 AIS 易感性产生协同作用。组合效应可以调节许多易感性多态性的最终生物学影响；因此，在比较不同人群的病例对照研究结果时应考虑这一点。
Study design. A genetic association study was performed on 126 patients with adolescent idiopathic scoliosis and 197 healthy controls from independent Hungarian pedigrees.Objective. To reveal implication of promoter polymorphisms of bone morphogenetic protein 4 (BMP4), interleukin-6 (IL6), leptin, matrix metalloproteinase-3 (MMP3), melatonin 1B receptor (MTNR1B) genes in adolescent idiopathic scoliosis (AIS). Combinatorial association of these candidate genes was also studied to detect additive effect of certain single-nucleotide polymorphism (SNP) patterns.Summary of Background Data. It was previously unraveled that IL6, MMP3, and MTNR1B genes could be considered as predisposition genes of AIS. Since BMP4 and leptin play a central role in bone formation and remodeling and are in direct interaction with melatonin, IL6, and MMP3, these also can be potential predisposition genes.Methods. The genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism.Results. At a single gene level, no significant differences were found for allele and genotype frequencies of the polymorphisms of these genes between cases or controls; therefore, the formerly detected association of IL6, MMP3, and MTNR1B with AIS was not confirmed in the Hungarian population by independent SNP analysis. However, significantly increased AIS risk was observed at particular combinations of genotypes of paired SNPs of the candidate genes.Conclusions. The genetic effect of promoter polymorphisms of BMP4, IL6, leptin, MMP3, and MTNR1B can be synergistic for susceptibility to AIS. The combinatorial effect can modulate the final biological impact of many susceptibility polymorphisms; therefore, this should be considered at the comparison of results from case-control studies of different populations.