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Genetic interactions model among Eotaxin gene polymorphisms in asthma
Authors:June-Hyuk Lee  Jason H. Moore  Sung-Woo Park  An-Soo Jang  Soo-Taek Uh  Yong Hoon Kim  Choon-Sik Park  Byung Lae Park  Hyoung Doo Shin
Affiliation:Department of Internal Medicine, Genome Research Center for Allergy and Respiratory Diseases, SoonChunHyang University Bucheon Hospital, Gyeonggi Do, 420-021, South Korea.
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. Gene–gene 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.
Keywords:Asthma  Epistasis  Polymorphism  Eotaxin
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