Genotype combinations of two IL4 polymorphisms influencing IL-4 plasma levels are associated with different risks of severe malaria in the Malian population.
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(-6)). 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.
INSERM, Génétique et Immunologie des Maladies Parasitaires, UMR 906, 27 Bvd Jean Moulin, 13385, Marseille, France.
Sandrine
S
Cabantous
Stéphane
S
Ranque
Belco
B
Poudiougou
Abdoulaye
A
Traore
Sofiane
S
Berbache
Joana
J
Vitte
Pierre
P
Bongrand
Ogobara
O
Doumbo
Alain J
AJ
Dessein
Laurent
L
Abel
Sandrine
S
Marquet
D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D015847:Interleukin-4 / Q000097:blood / Q000235:genetics*; D008288:Malaria / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D008302:Mali; D018598:Minisatellite Repeats / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D015847:Interleukin-4