IL3 variant on chromosomal region 5q31-33 and protection from recurrent malaria attacks
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IL3 variant on chromosomal region 5q31-33 and protection from recurrent malaria attacks. / Meyer, Christian G; Calixto Fernandes, Maria H; Intemann, Christopher D; Kreuels, Benno; Kobbe, Robin; Kreuzberg, Christina; Ayim, Matilda; Ruether, Andreas; Loag, Wibke; Ehmen, Christa; Adjei, Samuel; Adjei, Ohene; Horstmann, Rolf D; May, Jürgen.
in: HUM MOL GENET, Jahrgang 20, Nr. 6, 15.03.2011, S. 1173-81.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - IL3 variant on chromosomal region 5q31-33 and protection from recurrent malaria attacks
AU - Meyer, Christian G
AU - Calixto Fernandes, Maria H
AU - Intemann, Christopher D
AU - Kreuels, Benno
AU - Kobbe, Robin
AU - Kreuzberg, Christina
AU - Ayim, Matilda
AU - Ruether, Andreas
AU - Loag, Wibke
AU - Ehmen, Christa
AU - Adjei, Samuel
AU - Adjei, Ohene
AU - Horstmann, Rolf D
AU - May, Jürgen
PY - 2011/3/15
Y1 - 2011/3/15
N2 - Using segregation analyses, control of malaria parasites has previously been linked to a major gene within the chromosomal region 5q31-33, but also to complex genetic factors in which effects are under substantial age-dependent influence. However, the responsible gene variants have not yet been identified for this chromosomal region. In order to perform association analyses of 5q31-33 locus candidate single nucleotide polymorphisms (SNPs), 1015 children were recruited at the age of 3 months and followed monthly until the age of 2 years in an area holoendemic for Plasmodium falciparum malaria in Ghana. Quantitative (incidence rates of malaria episodes) and qualitative phenotypes (i.e. 'more than one malaria episode' or 'not more than one malaria episode') were used in population- and family-based analyses. The strongest signal was observed for the interleukin 3 gene (IL3) SNP rs40401 (P = 3.4 × 10(-7), P(c)= 1.4 × 10(-4)). The IL3 genotypes rs40401(CT) and rs40401(TT) were found to exert a protective effect of 25% [incidence rate ratio (IRR) 0.75, P = 4.1 × 10(-5)] and 33% (IRR 0.67, P = 3.2 × 10(-8)), respectively, against malaria attacks. The association was confirmed in transmission disequilibrium tests (TDT, qTDT). The results could argue for a role of IL3 in the pathophysiology of falciparum malaria.
AB - Using segregation analyses, control of malaria parasites has previously been linked to a major gene within the chromosomal region 5q31-33, but also to complex genetic factors in which effects are under substantial age-dependent influence. However, the responsible gene variants have not yet been identified for this chromosomal region. In order to perform association analyses of 5q31-33 locus candidate single nucleotide polymorphisms (SNPs), 1015 children were recruited at the age of 3 months and followed monthly until the age of 2 years in an area holoendemic for Plasmodium falciparum malaria in Ghana. Quantitative (incidence rates of malaria episodes) and qualitative phenotypes (i.e. 'more than one malaria episode' or 'not more than one malaria episode') were used in population- and family-based analyses. The strongest signal was observed for the interleukin 3 gene (IL3) SNP rs40401 (P = 3.4 × 10(-7), P(c)= 1.4 × 10(-4)). The IL3 genotypes rs40401(CT) and rs40401(TT) were found to exert a protective effect of 25% [incidence rate ratio (IRR) 0.75, P = 4.1 × 10(-5)] and 33% (IRR 0.67, P = 3.2 × 10(-8)), respectively, against malaria attacks. The association was confirmed in transmission disequilibrium tests (TDT, qTDT). The results could argue for a role of IL3 in the pathophysiology of falciparum malaria.
KW - Child, Preschool
KW - Chromosomes, Human, Pair 5
KW - Female
KW - Genetic Variation
KW - Ghana
KW - Humans
KW - Immunity, Innate
KW - Infant
KW - Interleukin-3
KW - Malaria, Falciparum
KW - Male
KW - Plasmodium falciparum
KW - Polymorphism, Single Nucleotide
KW - Recurrence
U2 - 10.1093/hmg/ddq562
DO - 10.1093/hmg/ddq562
M3 - SCORING: Journal article
C2 - 21224257
VL - 20
SP - 1173
EP - 1181
JO - HUM MOL GENET
JF - HUM MOL GENET
SN - 0964-6906
IS - 6
ER -