Distribution of investigated RIPK2 haplotypes in clinically classified leprosy patients and controls.

<p>Distribution of investigated RIPK2 haplotypes in clinically classified leprosy patients and controls.</p

Investigated SNP variants in leprosy patients and controls.

<p>Investigated SNP variants in leprosy patients and controls.</p

Distribution of investigated <i>NOD2</i>, <i>RIPK2</i>, and <i>LRRK2</i> variants in clinically classified leprosy patients and controls.

<p>Distribution of investigated <i>NOD2</i>, <i>RIPK2</i>, and <i>LRRK2</i> variants in clinically classified leprosy patients and controls.</p

IL-4 Haplotype -590T, -34T and Intron-3 VNTR R2 Is Associated with Reduced Malaria Risk among Ancestral Indian Tribal Populations

<div><h3>Background</h3><p>Interleukin 4 (IL-4) is an anti-inflammatory cytokine, which regulates balance between T_H1 and T_H2 immune response, immunoglobulin class switching and humoral immunity. Polymorphisms in this gene have been reported to affect the risk of infectious and autoimmune diseases.</p> <h3>Methods</h3><p>We have analyzed three regulatory <em>IL-4</em> 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).</p> <h3>Results</h3><p>The <b><em>-</em></b>590T, <b><em>-</em></b>34T and intron-3 VNTR R2 alleles were found to be associated with reduced malaria risk (P<0.001 for <b><em>-</em></b>590C>T and <b><em>-</em></b>34C>T, and P = 0.003 for VNTR). These three alleles were in strong LD (r²>0.75) and the TTR2 (<b><em>-</em></b>590T, <b><em>-</em></b>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%).</p> <h3>Conclusions</h3><p>Our study suggests that the <em>IL-4</em> 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, <em>IL-4</em> TTR2 haplotype might be under positive selection.</p> </div

Characteristics of studied subjects segregated according to clinical classification.

<p>Characteristics of studied subjects segregated according to clinical classification.</p

Distribution of <i>IL-4</i> intron-3 VNTR polymorphism.

<p>A and B: genotype and allelic distribution between malaria case control groups, respectively; C and D: genotype and allelic distribution among caste, nomadic, tribe and ancestral tribe, respectively.</p

Genotype distribution of <i>IL-4</i> intron-3 VNTR polymorphism in four linguistic families of Indian populations.

<p>Genotype distribution of <i>IL-4</i> intron-3 VNTR polymorphism in four linguistic families of Indian populations.</p

Genotype and allele distribution of IL-4 intron-3 VNTR polymorphism, -34CT and -590CT in various groups of Indian population.

<p>ATP: ancestral tribal population.</p

Genotype comparison among various groups of malaria case control and population study in multiple stages.

*<p>OR = 3.566, 95% CI = 2.348–5.416;</p

Characteristics of studied subjects of various world populations.

<p>Characteristics of studied subjects of various world populations.</p