Li Wancheng, Dai Wenjing, Sun Jian, Zhang Wei, Jiang Yi, Ma Chunlan, Wang Chunmao, He Jie
Department of Respiratory Medicine, The First Affiliated Hospital of Chengdu Medical College Chengdu 610500, Sichuan, China.
Int J Clin Exp Med. 2015 Oct 15;8(10):19346-52. eCollection 2015.
To investigate the association between single nucleotide polymorphism (SNP) of peroxisome proliferator-activated receptors γ (PPAR γ) and additional gene-gene interactions on asthma risk.
A total of 882 subjects (602 males, 280 females), with a mean age of 61.3±14.8 years old, including 430 asthma patients and 452 normal subjects were selected in this study, including the genotyping of polymorphisms. Logistic regression was performed to investigate association between SNP and asthma. Generalized MDR (GMDR) was used to analysis the interaction among four SNP.
Asthma risk was significantly lower in carriers of Ala allele of the rs1805192 polymorphism than those with Pro/Pro (Pro/Ala+ Ala/Ala versus Pro/Pro, adjusted OR (95% CI)=0.70 (0.51-0.94). In addition, we also found a significant association between rs10865710 and asthma, asthma risk was significantly lower in carriers of G allele of the rs10865710 polymorphism than those with CC (CG+ GG versus CC, adjusted OR (95% CI)=0.68 (0.55-0.95). There was a significant three-locus model (P=0.0107) involving rs1805192, rs10865710 and rs709158, indicating a potential gene-gene interaction among rs1805192, rs10865710 and rs709158. Overall, the three-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 60.72% after covariates adjustment.
Our results support an important association of rs1805192 and rs10865710 with asthma, and additional interaction among rs1805192, rs10865710 and rs709158.
研究过氧化物酶体增殖物激活受体γ（PPARγ）单核苷酸多态性（SNP）与其他基因-基因相互作用对哮喘风险的影响。
本研究共选取882名受试者（男性602名，女性280名），平均年龄61.3±14.8岁，其中包括430例哮喘患者和452例正常受试者，并进行多态性基因分型。采用逻辑回归分析SNP与哮喘之间的关联。使用广义多因子降维法（GMDR）分析4个SNP之间的相互作用。
rs1805192多态性位点Ala等位基因携带者的哮喘风险显著低于Pro/Pro基因型者（Pro/Ala + Ala/Ala与Pro/Pro相比，校正比值比（95%可信区间）=0.70（0.51 - 0.94））。此外，我们还发现rs10865710与哮喘之间存在显著关联，rs10865710多态性位点G等位基因携带者的哮喘风险显著低于CC基因型者（CG + GG与CC相比，校正比值比（95%可信区间）=0.68（0.55 - 0.95））。存在一个涉及rs1805192、rs10865710和rs709158的显著三位点模型（P = 0.0107），表明rs1805192、rs10865710和rs709158之间存在潜在的基因-基因相互作用。总体而言，三位点模型的交叉验证一致性为10/10，在调整协变量后测试准确性为60.72%。
我们的研究结果支持rs1805192和rs10865710与哮喘之间存在重要关联，以及rs1805192、rs10865710和rs709158之间存在额外的相互作用。
