Zhao Xu, Xu Kang, Shi Hui, Cheng Jinluo, Ma Jianhua, Gao Yanqin, Li Qian, Ye Xinhua, Lu Ying, Yu Xiaofang, Du Juan, Du Wencong, Ye Qing, Zhou Ling
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China;
Department of Endocrinology, the Affiliated Changzhou Second Hospital, Nanjing Medical University, Changzhou, Jiangsu 213003, China;
J Biomed Res. 2014 Mar;28(2):114-22. doi: 10.7555/JBR.27.20120061. Epub 2013 Mar 20.
This study was aimed to explore the associations between the combined effects of several polymorphisms in the PPAR-γ and RXR-α gene and environmental factors with the risk of metabolic syndrome by back-error propagation artificial neural network (BPANN). We established the model based on data gathered from metabolic syndrome patients (n = 1012) and normal controls (n = 1069) by BPANN. Mean impact value (MIV) for each input variable was calculated and the sequence of factors was sorted according to their absolute MIVs. Generalized multifactor dimensionality reduction (GMDR) confirmed a joint effect of PPAR-γ and RXR-α based on the results from BPANN. By BPANN analysis, the sequences according to the importance of metabolic syndrome risk factors were in the order of body mass index (BMI), serum adiponectin, rs4240711, gender, rs4842194, family history of type 2 diabetes, rs2920502, physical activity, alcohol drinking, rs3856806, family history of hypertension, rs1045570, rs6537944, age, rs17817276, family history of hyperlipidemia, smoking, rs1801282 and rs3132291. However, no polymorphism was statistically significant in multiple logistic regression analysis. After controlling for environmental factors, A1, A2, B1 and B2 (rs4240711, rs4842194, rs2920502 and rs3856806) models were the best models (cross-validation consistency 10/10, P = 0.0107) with the GMDR method. In conclusion, the interaction of the PPAR-γ and RXR-α gene could play a role in susceptibility to metabolic syndrome. A more realistic model is obtained by using BPANN to screen out determinants of diseases of multiple etiologies like metabolic syndrome.
本研究旨在通过反向传播人工神经网络(BPANN)探讨PPAR-γ和RXR-α基因中多个多态性的联合效应与环境因素之间的关联以及与代谢综合征风险的关系。我们基于从代谢综合征患者(n = 1012)和正常对照(n = 1069)收集的数据,通过BPANN建立模型。计算每个输入变量的平均影响值(MIV),并根据其绝对MIV对因素序列进行排序。广义多因素降维法(GMDR)基于BPANN的结果证实了PPAR-γ和RXR-α的联合效应。通过BPANN分析,代谢综合征危险因素重要性的序列依次为体重指数(BMI)、血清脂联素、rs4240711、性别、rs4842194、2型糖尿病家族史、rs2920502、体力活动、饮酒、rs3856806、高血压家族史、rs1045570、rs-6537944、年龄、rs17817276、高脂血症家族史、吸烟、rs1801282和rs3132291。然而,在多因素logistic回归分析中,没有多态性具有统计学意义。在控制环境因素后,A1、A2、B1和B2(rs42407-11、rs4842194、rs2920502和rs3856806)模型是采用GMDR方法的最佳模型(交叉验证一致性10/10,P = 0.0107)。总之,PPAR-γ和RXR-α基因的相互作用可能在代谢综合征易感性中起作用。通过使用BPANN筛选出代谢综合征等多种病因疾病的决定因素,可获得更符合实际的模型。