ArticlePloS one2012
IL-4 haplotype -590T, -34T and intron-3 VNTR R2 is associated with reduced malaria risk among ancestral indian tribal populations.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Possible association of IL-4 VNTR polymorphism with susceptibility to preeclampsia.BioMed research international · 2014Trial
- Evolutionary Balancing of Genetic Consequence and Innovation in Mammals Through Variable Number Tandem Repeats.Genome biology and evolution · 2026Review
- [Immunomodulatory mechanism of umbilical cord mesenchymal stem cells modified by miR-125b-5p in systemic lupus erythematosus].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2024Article
- Genetics of Malaria Inflammatory Responses: A Pathogenesis Perspective.Frontiers in immunology · 2019Review
- NOS3 27-bp and IL4 70-bp VNTR Polymorphisms Do Not Contribute to the Risk of Sickle Cell Crisis.Turkish journal of haematology : official journal of Turkish Society of Haematology · 2016Article
- Hunter-gatherer genomics: evolutionary insights and ethical considerations.Current opinion in genetics & development · 2016Review
- Interleukin-1β (IL-1β) & IL-4 gene polymorphisms in patients with systemic lupus erythematosus (SLE) & their association with susceptibility to SLE.The Indian journal of medical research · 2016Article
- Genotype combinations of two IL4 polymorphisms influencing IL-4 plasma levels are associated with different risks of severe malaria in the Malian population.Immunogenetics · 2015Article
- Differential positive selection of malaria resistance genes in three indigenous populations of Peninsular Malaysia.Human genetics · 2015Article
- IL10A genotypic association with decreased IL-10 circulating levels in malaria infected individuals from endemic area of the Brazilian Amazon.Malaria journal · 2015Article
- Article
- MBL2 variations and malaria susceptibility in Indian populations.Infection and immunity · 2014Article
- Variations in ncRNA gene LOC284889 and MIF-794CATT repeats are associated with malaria susceptibility in Indian populations.Malaria journal · 2013Article
- Association of IL-4 and IL-10 maternal haplotypes with immune responses to P. falciparum in mothers and newborns.BMC infectious diseases · 2013Article
- Ocular manifestations of sickle cell disease and genetic susceptibility for refractive errors.Taiwan journal of ophthalmologyArticle
- Association Between IL-4 and IL-6 Expression Variants and Gastric Cancer Among Portuguese Population.GE Portuguese journal of gastroenterologyArticle
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Authors and funding
17 authors at 10 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInterleukin 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.
methodsWe 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).
resultsThe -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%).
conclusionsOur 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.
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