Zhang Qing-Guo, Zhang Jiao, Yu Pei, Shen Hao
Beijing, China From the Plastic Surgery Hospital, Chinese Academy of Medical Science.
Plast Reconstr Surg. 2009 Oct;124(4):1157-1164. doi: 10.1097/PRS.0b013e3181b454d8.
The objectives of this study were to filter out the environmental and genetic risk factors in microtia patients and to demonstrate the relationship between environmental and inherited factors in congenital microtia.
A case-control study was carried out in 121 congenital microtia patients and 152 controls. Epidemiologic data related to environmental exposure were gathered through personal interviews with the target group. Polymerase chain reaction and DNA sequence analysis were performed to analyze the Gsc gene and BMP5 gene mutation in the case and control groups. The logistic regression model was used to analyze environmental and genetic risk factors and their relationships to microtia.
The main risk factors were disease during pregnancy (odds ratio, 5.890; 95 percent CI, 2.358 to 14.715), toxicity exposure during pregnancy (odds ratio, 4.764; 95 percent CI, 1.659 to 13.680), and resident area (odds ratio, 5.114; 95 percent CI, 2.086 to 12.535). The synthetic attributable risks amount to 0.7185. As to the Gsc gene, six of these patients had a same-sense mutation C-->T on 197 bp in exon 2; a missense mutation on A-->G 125 bp in exon 3 occurred in two cases; and amino acid changes from glutamic acid to glutamine. A heterozygosity on 196 TTT-->ACA resulting in missense mutation was detected in four patients, causing the amino acid to change from phenylalanine to threonine in BMP5 maternal peptide gene. However, no mutations were detected in the control subjects.
The results suggested that both environmental and genetic factors contribute to congenital microtia. The Gsc gene and the BMP5 maternal peptide gene may act as the predisposing genes of microtia. Further research is needed to clarify the relationship between the risk factors and microtia.
本研究的目的是筛选出小耳畸形患者的环境和遗传风险因素,并阐明先天性小耳畸形中环境因素与遗传因素之间的关系。
对121例先天性小耳畸形患者和152例对照进行病例对照研究。通过对目标群体进行个人访谈收集与环境暴露相关的流行病学数据。对病例组和对照组进行聚合酶链反应和DNA序列分析,以分析Gsc基因和BMP5基因突变情况。采用逻辑回归模型分析环境和遗传风险因素及其与小耳畸形的关系。
主要风险因素为孕期患病(比值比,5.890;95%可信区间,2.358至14.715)、孕期接触毒性物质(比值比,4.764;95%可信区间,1.659至13.680)和居住地区(比值比,5.114;95%可信区间,2.086至12.535)。综合归因风险为0.7185。对于Gsc基因,这些患者中有6例在第2外显子197 bp处发生同义突变C→T;2例在第3外显子125 bp处发生错义突变A→G,氨基酸由谷氨酸变为谷氨酰胺。在4例患者中检测到196 TTT→ACA处的杂合性导致错义突变,使BMP5母源肽基因中的氨基酸由苯丙氨酸变为苏氨酸。然而,在对照组中未检测到突变。
结果表明环境因素和遗传因素均与先天性小耳畸形有关。Gsc基因和BMP5母源肽基因可能是小耳畸形的易感基因。需要进一步研究以阐明风险因素与小耳畸形之间的关系。