Pierre Candelaria

Disparity of innate immunity–related gene effects on asthma and allergy on Karelia

To cite this article: Zhang G, Candelaria P, Mäkelä JM, Khoo S‐K, Hayden MC, von Hertzen L, Laatikainen T, Vartiainen E, Goldblatt J, Haahtela T, LeSouëf NP. Disparity of innate immunity–related gene effects on asthma and allergy on Karelia. Pediatr Allergy Immunol 2011; 22: 621–630.

Interleukin-10 (IL-10) polymorphisms are associated with IL-10 Production and clinical malaria in young children

ABSTRACT The role of interleukin-10 (IL-10) in malaria remains poorly characterized. The aims of this study were to investigate (i) whether genetic variants of the IL-10 gene influence IL-10 production and (ii) whether IL-10 production as well as the genotypes and haplotypes of the IL-10 gene in young children and their mothers are associated with the incidence of clinical malaria in young children. We genotyped three IL-10 single nucleotide polymorphisms in 240 children and their mothers from a longitudinal prospective cohort and assessed the IL-10 production by maternal peripheral blood mononuclear cells (PBMCs) and cord blood mononuclear cells (CBMCs). Clinical episodes of Plasmodium falciparum malaria in the children were documented until the second year of life. The polymorphism IL-10 A-1082G (GCC haplotype of three SNPs in IL-10) in children was associated with IL-10 production levels by CBMC cultured with P. falciparum-infected erythrocytes (P = 0.043), with the G allele linked to low IL-10 production capacity. The G allele in children was also significantly associated with a decreased risk for clinical malaria infection in their second year of life (P = 0.016). Furthermore, IL-10 levels measured in maternal PBMCs cultured with infected erythrocytes were associated with increased risk of malaria infection in young children (P < 0.001). In conclusion, IL-10 polymorphisms and IL-10 production capacity were associated with clinical malaria infections in young children. High IL-10 production capacity inherited from parents may diminish immunological protection against P. falciparum infection, thereby being a risk for increased malaria morbidity.

Disparity of innate immunity-related gene effects on asthma and allergy on Karelia

To cite this article: Zhang G, Candelaria P, Mäkelä JM, Khoo S‐K, Hayden MC, von Hertzen L, Laatikainen T, Vartiainen E, Goldblatt J, Haahtela T, LeSouëf NP. Disparity of innate immunity–related gene effects on asthma and allergy on Karelia. Pediatr Allergy Immunol 2011; 22: 621–630.

Evolution and respiratory genetics

Evolution is a plausible explanation for between-population differences in particular allele frequencies if: the genes involved have related functions; the heterogeneous alleles involved have similar functional consequences; the involved genes are not linked chromosomally; and the patterns observed would result in a biologically plausible, survival-enhancing gene–environment interaction. However, possible evolutionary effects have to be differentiated from founder effects and random genetic drift. The current authors have noted the existence of a consistent pattern of allelic frequencies in genes related to T-helper 2 (Th2) immune responses in humans of different ancestral backgrounds, residing in climatically similar regions. Th2 responses are thought to have evolved in mammals to resist infection by parasites, particularly helminths. Modern man arose in tropical Africa where helminths thrived. Relatively recently, humans migrated to cooler or drier climates where most helminths struggled to reproduce. The genetic tendency to strong Th2 responses may have become a health liability, the reduction in risk from parasites being counterbalanced by an increased inherited propensity to atopic or allergic diseases. The pattern noted by the present authors includes specific alleles of interleukin-4 and its receptor, interleukin-13, interleukin-10, the β chain of the high-affinity receptor for immunoglobulin E, the β1-adrenergic receptor, and the alpha chain of tumour necrosis factor. These population-specific polymorphism profiles are likely to be relevant in current disease patterns. The high incidence of asthma in migrants from tropical locations to affluent temperate countries is likely to be related to these patterns. Of even more concern is the possibility that increasing westernisation among the ∼2 billion people living in the tropics will produce rapidly increasing levels of asthma, as these populations have a high genetic predisposition to allergic disease.

The importance of environment on respiratory genotype/phenotype relationships in the Inuit.

To cite this article: Candelaria PV, Backer V, Khoo S‐K, Bizzintino JA, Hayden CM, Baynam G, Laing IA, Zhang G, Porsbjerg C, Goldblatt J, LeSouëf PN, The Greenlandic Study Population Group. The importance of environment on respiratory genotype/phenotype relationships in the Inuit. Allergy 2010; 65: 229–237.