Differential cytokine genotype frequencies among Canadian Aboriginal and Caucasian populations

Abstract

Genetic diversity related to the human immune response is a key factor in individual and population survival throughout human history. Population diversity in disease susceptibility and resistance have been identified and linked to differences in cytokine mRNA and protein expression levels. Polymorphisms in the regulatory regions of cytokine genes can influence gene transcription levels and they have been associated with susceptibility to, and/or severity of, autoimmune disorders such as rheumatoid arthritis, meningococcus and sepsis. It is reported here that in two study populations, Canadian Aboriginal individuals have a higher frequency of cytokine single-nucleotide polymorphisms favouring a low production of TNFa, IFNg and IL-10 and high production of IL-6 as compared to a Caucasian population. We postulate that the evolution of this unique cytokine genotype profile may be linked to the Aboriginal adaptation to selection pressures related to an environment in which helminthic, parasitic and fungal infections predominated.

Concordance between IFNγ gene +874 A/T polymorphism and interferon-γ expression in a TB-endemic indigenous setting

“…This comparison additionally reveals that the IFNG +874 A/T polymorphism is significantly associated with pulmonary TB, the findings showed that indigenous homozygous for the +874 A allele had a 3.59-fold increased risk of contracting TB. Our results correlate with previous findings showing that individuals homozygous for the +874 A allele had a 3.75-fold increased risk of developing TB and the lowest IFNG expression level in the groups studied, therefore supporting that the IFNG +874 A/T polymorphism is significantly associated with pulmonary TB 18,19 .…”

“…The latter population was used for comparison because of the historical context in which the two populations evolved in relationship to their microbial environments, particularly in the context of their response to the selective pressures of their respective microbial environments, as found by Larcombe et al 18 .…”

“…Accordingly, several studies of genetic diversity in ethnic populations have reported an association between the IFNG +874 polymorphism and TB 18,25 . Studies in relation to genotype profile in Canadian aboriginal and Filipino populations showed that both populations have a higher frequency of cytokine SNPs associated with low production of IFNG (AA genotype) compared with white Americans; these aboriginal populations exhibited a significantly higher frequency of the A allele at the IFNG loci 18 ; in contrast, white Americans exhibit a relatively higher frequency of cytokine SNPs associated with delayed-type hypersensitivity IFN-γ response, the latter suggest that white Americans tend to mount a Th1 immune response, while Canadian aboriginal and Filipino populations show a tendency towards a Th2 immune response 18 . In this context, intestinal parasites are endemic among the Warao population, which is consistent with the considerably higher levels of total serum IgE found in this population 26 .…”

“…The IFN-γ cytokine is the archetypical readout for cell-mediated immune response (CMI) assays 16 , and has been recognized as the defining cytokine of Th1 cells. IFN-γ-mediated immune activation appears to play an important role in immunity to intracellular pathogens, both in mice and humans [17][18][19] . Early studies demonstrated that mice with disruption of IFNG are more susceptible to infection by M. tuberculosis than wild-type strains 20 population, who live in Brazil and exhibit high TB prevalence, and revealed that the absence of TST response (anergy) may be associated with a predominantly Th2 cytokine pattern, which may increase susceptibility to TB 21 .…”

Polimorfismos de la región promotora del gen de la IL-10 y artritis reumatoide en una población colombiana

“…La influencia de factores desconocidos de tipo ambiental o genético en la segregación de los alelos, que pudieran enmascarar la detección del efecto del polimorfismo en esta población, podría considerarse como posible explicación. Estos factores pueden estar relacionados con presión selectiva hacia una respuesta inmune más efectiva frente a un ambiente con alta prevalencia de agentes infecciosos (55,56), o a la existencia de desequilibrio de ligamiento con otras variantes polimórficas existentes en la región promotora del gen (42,46).…”