Association of IL‐4 589 C/T promoter and IL‐4RαI50V receptor polymorphism with susceptibility to HIV‐1 infection in North Indians

Abstract

The clinical course and outcome of HIV-1 infection are highly variable among individuals. Interleukin 4 (IL-4) is a key T helper 2 cytokine with various immune-modulating functions including induction of immunoglobulin E (IgE) production in B cells, downregulation of CCR5 and upregulation of CXCR4, the main co-receptors for HIV. Our objective is to investigate whether single-nucleotide polymorphisms (SNPs) in the IL-4 promoter 589 C/T and IL-4 Ralpha I50V affect the susceptibility to HIV infection and its progression to AIDS in North Indian individuals. The study population consisted of 180 HIV-1 seropositive (HSP) stratified on the basis of disease severity (stage I, II, III), 50 HIV-1 exposed seronegative (HES), and 305 HIV-1 seronegative (HSN) individuals. The subjects were genotyped for IL-4 589 C/T promoter polymorphism and IL-4 Ralpha I50V by polymerase chain reaction restriction fragment length polymorphism. The results showed that IL-4 589 C/T was not associated with the risk of HIV infection and disease progression. However, the IL-4Ralpha I50 allele and genotype was significantly increased in HSP compared to HSN and HSP and was associated with risk of HIV infection. The frequency of IL-4Ralpha I50 allele in the HSP group was higher than in HSN (76.11 vs. 64.75%; P = 0.000; OR = 1.734) and HES (76.11% vs. 62.00%; P = 0.007; OR = 1.953). Homozygous IL-4Ralpha I50I genotype was significantly increased in HSP group compared with HSN (58.88% vs. 44.26%; P = 0.002; OR = 1.804) and HES (58.88% vs. 42.00%; P = 0.038; OR = 1.978). The present study for the first time suggests an association of IL-4Ralpha I50 allele with increased likelihood of HIV-1 infection in North Indian population. Further studies are required to confirm these findings and understand the effect of IL-4Ralpha polymorphism on the outcome of HIV-1 infection.

The Effects of Gene Polymorphisms in Interleukin-4 and Interleukin-6 on the Susceptibility of Rheumatoid Arthritis in a Chinese Population

“…In humans the IL-4 gene has been mapped to chromosome 14q32 [34]. The IL-4 gene promoter contains a number of polymorphic loci, which were reported to influence the susceptibility of many diseases, including the IL-4-33C/T [35], IL-4-589C/T [36], and IL-4-590C/T [20, 37, 38]; especially, the genotype and allele frequencies of IL-4-590C/T were well studied and reported to be associated with many diseases, such as rheumatoid arthritis [3, 20], liver disease [37], and gastric cancer [38]. To our surprise, although the role of the genotype and allele frequencies of IL-4-590C/T in association with rheumatoid arthritis has been documented, we did not find any reports with regard to the genetic polymorphisms of IL-4-590C/T with rheumatoid arthritis in Chinese population.…”

Expression of γ‐chain cytokine receptors on CD8+ T cells in HIV infection with a focus on IL‐7Rα (CD127)

“…Slow disease progression was associated with homozygous expression of the V50 single‐nucleotide polymorphism of IL‐4Rα, whereas exon 12 U‐haplotypes were associated with either susceptibility or resistance to HIV by parental route of infection or sexual exposure, respectively 112 . A recent study of HIV + North Indians identified that the I50 allele of IL‐4Rα was linked to disease susceptibility and progression 113 . This would suggest that the I50 allele may contribute to the observed enhanced IL‐4‐induced Th2 responses that have been associated with the development of AIDS 114 …”

Association of IL‐4 −590 T>C polymorphism and risk of renal cell carcinoma in a Chinese population

“…Genomic DNA was isolated from leucocytes of venous blood by proteinase K digestion and phenol ⁄ chloroform extraction. The IL-4 )590 T>C polymorphism was determined by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, as described previously (Chatterjee et al, 2009). The PCR primers for the IL-4 )590 T>C polymorphism were 5¢-TAAACTTGGGAGAA-CATGGT-3¢ (forward) and 5¢-TGGGGAAAGATA-GAGTAATA-3¢ (reverse).…”