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- Title
Genotype combinations of two IL4 polymorphisms influencing IL-4 plasma levels are associated with different risks of severe malaria in the Malian population.
- Authors
Cabantous, Sandrine; Ranque, Stéphane; Poudiougou, Belco; Traore, Abdoulaye; Berbache, Sofiane; Vitte, Joana; Bongrand, Pierre; Doumbo, Ogobara; Dessein, Alain.; Abel, Laurent; Marquet, Sandrine
- Abstract
We have previously found that children heterozygous for IL4 variable-number tandem repeat (VNTR) (rs8179190) or IL4-33 (rs2070874) variants were at risk for severe malaria (SM), whereas homozygous children were protected suggesting a complex genetic control. Hence, to dissect this complex genetic control of IL4 VNTR and IL4-33, we performed further investigation by conditional logistic regression analysis and found a strong interaction between both markers ( p < 10). The best-fit model revealed three genotype combinations associated with different levels of SM risk. The highest risk (odds ratio (OR) = 4.8, 95 % confidence interval (CI) = 2.0-11.5) was observed for subjects carrying at least one copy of both IL4-33 allele T and IL4 VNTR allele 1, who exhibited higher interleukin (IL)-4 plasma levels ( p = 0.007). Children homozygous for IL4 VNTR allele 2 had a lower SM risk as well as lower IL-4 plasma levels. Our findings indicate that the genetic interaction between these two IL-4 variants is a key factor of SM susceptibility, probably because of its direct role in IL-4 regulation.
- Subjects
GENETIC polymorphisms; MALIANS; MALARIA; TANDEM repeats; GENETICS
- Publication
Immunogenetics, 2015, Vol 67, Issue 5/6, p283
- ISSN
0093-7711
- Publication type
Article
- DOI
10.1007/s00251-015-0836-3