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IL-4 haplotype -590T, -34T and intron-3 VNTR R2 is associated with reduced malaria risk among ancestral indian tribal populations.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (10), pp. e48136. Date of Electronic Publication: 2012 Oct 24. - Publication Year :
- 2012
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Abstract
- Background: Interleukin 4 (IL-4) is an anti-inflammatory cytokine, which regulates balance between T(H)1 and T(H)2 immune response, immunoglobulin class switching and humoral immunity. Polymorphisms in this gene have been reported to affect the risk of infectious and autoimmune diseases.<br />Methods: We have analyzed three regulatory IL-4 polymorphisms; -590C>T, -34C>T and 70 bp intron-3 VNTR, in 4216 individuals; including: (1) 430 ethnically matched case-control groups (173 severe malaria, 101 mild malaria and 156 asymptomatic); (2) 3452 individuals from 76 linguistically and geographically distinct endogamous populations of India, and (3) 334 individuals with different ancestry from outside India (84 Brazilian, 104 Syrian, and 146 Vietnamese).<br />Results: The -590T, -34T and intron-3 VNTR R2 alleles were found to be associated with reduced malaria risk (P<0.001 for -590C>T and -34C>T, and P = 0.003 for VNTR). These three alleles were in strong LD (r²>0.75) and the TTR2 (-590T, -34T and intron-3 VNTR R2) haplotype appeared to be a susceptibility factor for malaria (P = 0.009, OR = 0.552, 95% CI = 0.356 -0.854). Allele and genotype frequencies differ significantly between caste, nomadic, tribe and ancestral tribal populations (ATP). The distribution of protective haplotype TTR2 was found to be significant (χ²₃ = 182.95, p-value <0.001), which is highest in ATP (40.5%); intermediate in tribes (33%); and lowest in caste (17.8%) and nomadic (21.6%).<br />Conclusions: Our study suggests that the IL-4 polymorphisms regulate host susceptibility to malaria and disease progression. TTR2 haplotype, which gives protection against malaria, is high among ATPs. Since they inhabited in isolation and mainly practice hunter-gatherer lifestyles and exposed to various parasites, IL-4 TTR2 haplotype might be under positive selection.
- Subjects :
- Adolescent
Adult
Base Sequence
Brazil
Female
Gene Frequency
Genetic Predisposition to Disease ethnology
Genetic Predisposition to Disease genetics
Genotype
Humans
India
Malaria, Falciparum ethnology
Male
Middle Aged
Molecular Sequence Data
Risk Factors
Sequence Homology, Amino Acid
Syria
Vietnam
Young Adult
Haplotypes
Interleukin-4 genetics
Introns genetics
Malaria, Falciparum genetics
Minisatellite Repeats genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23110190
- Full Text :
- https://doi.org/10.1371/journal.pone.0048136