Specific polymorphisms of cytokine genes are associated with different risks to develop single-system or multi-system childhood Langerhans cell histiocytosis.
Cytokines and chemokines determine mobilisation of Langerhans cells and their dysregulation is implicated in the pathogenesis of Langerhans cell histiocytosis (LCH). Twenty point mutations of 12 different cytokine genes were studied in 41 Italian children, 15 with single-system (SS) and 26 with multi-system disease. The allele and genotype distributions of interleukin-4 (IL-4) and interferon-gamma (IFNgamma) were significantly different in patients vs. 140 controls (P = 0.007, and P = 0.018). Older children with single-system disease shared the 'anti-inflammatory profile' determined by the intermediate producer genotype IFNgamma +874A/T (P = 0.029) and the high-producer genotypes IL-4 -590C/T and T/T (P = 0.029). Our findings suggest that specific cytokine gene variants affect susceptibility to LCH and its clinical heterogeneity.
De Filippi
Paola
P
Genetica Medica, Università di Pavia and I.R.C.C.S. Policlinico San Matteo, Pavia, Italy.
Badulli
Carla
C
Cuccia
Mariaclara
M
De Silvestri
Annalisa
A
Dametto
Ennia
E
Pasi
Annamaria
A
Garaventa
Alberto
A
del Prever
Adalberto Brach
AB
Todesco
Alessandra
A
Trizzino
Antonino
A
Danesino
Cesare
C
Martinetti
Miryam
M
Aricò
Maurizio
M
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006646:Histiocytosis, Langerhans-Cell / Q000235:genetics*; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D008297:Male; D017354:Point Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D016207:Cytokines; D007375:Interleukin-1; D015847:Interleukin-4; D007371:Interferon-gamma