TY - JOUR
T1 - Joint influences of Acidic-Mammalian-Chitinase with Interleukin-4 and Toll-like receptor-10 with Interleukin-13 in the genetics of asthma
AU - Heinzmann, Andrea
AU - Brugger, Markus
AU - Bierbaum, Sibylle
AU - Mailaparambil, Beena
AU - Kopp, Matthias V.
AU - Strauch, Konstantin
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2010/6
Y1 - 2010/6
N2 - In the genetics of asthma, single genetic polymorphisms confer only a small individual risk factor. Haplotype-based association analyses, including joint analyses of several candidate genes, might therefore yield more convincing results than single-region statistics. We set out to test for joint influences of asthma genes previously identified in our study population that is acidic mammalian chitinase (AMCase), Toll-like receptor (TLR)-10, and the interleukins IL-4, IL-13, IL-8, and IL-15. In particular, we investigated whether haplotypes at two or three genes show stronger association with the trait than at a single gene alone. We genotyped 26 polymorphisms in 321 asthmatic children and 270 controls. Haplotype-based association analyses were performed by the program FAMHAP. Single-, two-, and three-gene analyses were conducted as well as conditional analyses for pairs of genes. In the two-region analyses, best evidence was found for a joint effect on asthma for AMCase and IL-4 (praw<5×10-7) as well as AMCase and IL-13 (praw=5×10-7). Besides, IL-13 and TLR-10 showed a stronger two-gene result (praw=0.001607) than the respective single-gene analyses. Conditional analyses yielded similar results for these two-gene combinations and also revealed mutual additional effects for IL-13 and IL-4 (pstratified=0.014831 and 0.001525, respectively). The most significant results demonstrate a joint effect of AMCase with IL-4 or IL-13 on the trait. Furthermore, additional mutual effects were seen for AMCase and IL-4 as well as for TLR-10 and IL-13. The corresponding pathways might therefore be of particular importance in the genetics of asthma. Further studies are needed to elucidate the functional importance of these gene-gene effects and their precise role in asthma pathogenesis.
AB - In the genetics of asthma, single genetic polymorphisms confer only a small individual risk factor. Haplotype-based association analyses, including joint analyses of several candidate genes, might therefore yield more convincing results than single-region statistics. We set out to test for joint influences of asthma genes previously identified in our study population that is acidic mammalian chitinase (AMCase), Toll-like receptor (TLR)-10, and the interleukins IL-4, IL-13, IL-8, and IL-15. In particular, we investigated whether haplotypes at two or three genes show stronger association with the trait than at a single gene alone. We genotyped 26 polymorphisms in 321 asthmatic children and 270 controls. Haplotype-based association analyses were performed by the program FAMHAP. Single-, two-, and three-gene analyses were conducted as well as conditional analyses for pairs of genes. In the two-region analyses, best evidence was found for a joint effect on asthma for AMCase and IL-4 (praw<5×10-7) as well as AMCase and IL-13 (praw=5×10-7). Besides, IL-13 and TLR-10 showed a stronger two-gene result (praw=0.001607) than the respective single-gene analyses. Conditional analyses yielded similar results for these two-gene combinations and also revealed mutual additional effects for IL-13 and IL-4 (pstratified=0.014831 and 0.001525, respectively). The most significant results demonstrate a joint effect of AMCase with IL-4 or IL-13 on the trait. Furthermore, additional mutual effects were seen for AMCase and IL-4 as well as for TLR-10 and IL-13. The corresponding pathways might therefore be of particular importance in the genetics of asthma. Further studies are needed to elucidate the functional importance of these gene-gene effects and their precise role in asthma pathogenesis.
UR - http://www.scopus.com/inward/record.url?scp=77956234325&partnerID=8YFLogxK
U2 - 10.1111/j.1399-3038.2010.01053.x
DO - 10.1111/j.1399-3038.2010.01053.x
M3 - Journal articles
C2 - 20444155
AN - SCOPUS:77956234325
SN - 0905-6157
VL - 21
SP - e679-e686
JO - Pediatric Allergy and Immunology
JF - Pediatric Allergy and Immunology
IS - 4 PART2
ER -