Genetic interactions model among Eotaxin gene polymorphisms in asthma

Abstract

Eotaxin family (Eotaxin 1,2 and 3) recruits and activates CCR3-bearing cells such as eosinophil, mast cells, and Th2 lymphocytes that play a major role in allergic disorders. We examined the polygenetic effects of the Eotaxin gene family in a Korean population. Genegene interactions were tested using a multistep approach with multifactor dimensionality reduction (MDR) method between asthmatics and normal controls. The overall best MDR model of the main effect single nucleotide polymorphisms (SNPs) included EOT2 + 1272A [ G and EOT3 + 77C [ T (model 1) [testing accuracy 0.597, cross-validation consistency (CVC) 10/10, P \ 0.001]. The overall best MDR model of the SNPs with no main effects included EOT2 + 304C [ A, EOT3 + 716A [ G, and EOT3 + 1579G [ A (model 2) (testing accuracy 0.616, CVC 10/10, P \ 0.001). Model 3 was obtained by including the MDR variables for models 1 and 2. This new composite model predicted asthma with better accuracy than either model 1 or model 2 (testing accuracy 0.643, CVC 10/10, P \ 0.001). The detection of statistical interaction models is one evidence of gene-gene interactions among Eotaxin genes, and this interaction is thought to influence the development of asthma. Although the models are limited to determining statistical interactions within a population, they may be useful for identifying groups at high risk of developing asthma.

Association of three-gene interaction among MTHFR, ALOX5AP and NOTCH3 with thrombotic stroke: a multicenter case–control study

“…The accuracy of the three-locus model without covariate adjustment was similar to that with adjustment ( Table 6). The entropy analysis proposed by Dr. Moore et al (2006) is used to facilitate interpretation of the results in recent papers (Lee et al 2008). After the analysis, we have more information for the interpretation of this three-locus model.…”

Gene - Gene Interactions AmongMCPGenes Polymorphisms in Asthma

“…The subjects are at high risk only when the threshold ratio exceeds 1.0. When the final best model was selected, a model for high- and low-risk genotype combinations was formed using an adjusted threshold that was equal to the ratio of cases and controls in a model that maximizes the cross-validation consistency (CVC) 19,20. Accuracy is defined as the proportion of subjects that are grouped correctly according to their case-control status.…”

Unraveling the complex genetic underpinnings of asthma and allergic disorders

“…These genes include defensin-b1 (an antimicrobial peptide), uteroglobin/Clara cell 16-kD protein (CC16) (an inhibitor of Th2-cell differentiation), and several chemokines (CCL-5, CCL-11, CCL-24, and CCL-26) involved in the recruitment of T-cells and eosinophils [13][14][15][16][17][18][19]. Variations in SPINK5, a serine protease inhibitor limited to the epithelium, have been associated with asthma, but with conflicting results [20][21][22][23]24 ].…”