Association between genes encoding components of the IL-4/IL-4 receptor pathway and dermatitis in children

Objective

To determine whether IL-4, IL-4Rα and STAT6 polymorphisms are associated with susceptibility to dermatitis in Egyptian children.

Methods

We genotyped three groups of children, consisting of 106 atopic dermatitis (AD) children, 95 non-AD children, and 100 of healthy controls, for IL-4 (− 590 C/T), (− 33 C/T), IL-4Rα (I50V), (Q576R) and STAT6 (2964 G/A), (2892 C/T) gene polymorphisms using PCR-RFLP assay. Total serum IgE and serum IL-4 levels were detected by ELISA.

Results

There was a non-significant association of IL-4 − 590 C/T, − 33 C/T polymorphisms in the children with non-AD or those with AD when compared with the controls. We identified a significant association between IL-4Rα I50V, Q576R polymorphisms and dermatitis susceptibility in AD (p = 0.002, < 0.001 respectively), whereas no such association was observed in non-AD group (p = 0.52, 0.99 respectively). A significant association between STAT6 polymorphisms and both types of dermatitis was found. Patients who were carriers of IL4 − 590C, IL-4Rα I50V G, STAT6 2964 A and STAT6 2892 T had an increased risk of AD [OR and 95% CI: 3.2 (2.5–4.2), p = 0.005]. Furthermore, there was no relation between each polymorphism and serum IL-4 level (p > 0.05 for each) while homozygosity for the risk alleles of IL-4, IL-4Rα and STAT6 SNPs were significantly associated with increased total IgE levels in all subjects.

Conclusion

In Egyptian children, the IL-4Rα and the STAT6 polymorphism may play a role in susceptibility to AD. In addition, gene–gene interaction between the IL-4, the IL-4Rα and the STAT6 significantly increases an individual's susceptibility to AD.     

Influence of functional genetic polymorphism (-590C/T) in non-small cell lung cancer (NSCLC) development: the paradoxal role of IL-4

Lung cancer is the leading cause of death by cancer in the world, originating about 17.5% of total deaths from cancer (1.18 million). Inflammation plays an important role in the pathogenesis of lung cancer. IL-4 is an anti-inflammatory cytokine, which reduces the production of proinflammatory cytokines by monocytes and with direct antiproliferative effects in some tumors. The polymorphism -590C/T SNP is a C to T transition in the -590 position of the promoter region of the IL-4 gene. The aim of this study was to evaluate the influence of this polymorphism in the susceptibility to NSCLC. DNA was extracted from peripheral blood of 1060 individuals (391 patients diagnosed with NSCLC and a control group of 669 individuals without cancer). The characterization of IL-4 -590C/T genotypes was performed by PCR-RFLP (BsmFI). The -590C/T polymorphism genotypes were classified as low (CC) and high expression (TT). The frequencies obtained for the CC and TT genotypes were 90.1% and 9.9%, respectively, in the control group and 92.9% and 7.1%, respectively, in the case group. The analysis of the TT and CC genotype frequencies in the two groups showed a statistically significant difference in its distribution, indicating a protection of 80% for the development of NSCLC, type epidermoid in individuals with the TT genotype when compared with individuals with CC genotype (P=0.024, OR=0.221: 95% CI=0.053-0.928). We present for the first time that increased expression of IL-4 associated with the TT genotype may contribute to immune surveillance during NSCLC development.     

V75R576 IL-4 receptor alpha is associated with allergic asthma and enhanced IL-4 receptor function

Asthma is a complex polygenic disease. Many studies have implicated the importance of IL-4R alpha in the development of allergic inflammation and its gene has been implicated in the genetics of asthma and atopy. In this study, we examined the functional consequences of two of the human IL-4R alpha allelic variants that have been found to associate with asthma and atopy. We examined the effects of each variant alone and in combination on IL-4-dependent gene induction. We found that neither the Q576R nor the I75V variants affected IL-4-dependent CD23 expression. However, the combination of V75R576 resulted in expression of an IL-4R alpha with enhanced sensitivity to IL-4. We next examined the genetics of five of the known IL-4R alpha allelic variants in asthmatic and nonatopic populations. Strikingly, the association of V75/R576 with atopic asthma was greater than either allele alone and the association of R576 with atopic asthma was dependent on the coexistence of V75. A haplotype analysis revealed a single IL-4R alpha haplotype that was associated with allergic asthma, VACRS, further confirming the importance of the V75 and R576 combination in the genetics of asthma. This is the first report demonstrating that a functional alteration in IL-4R alpha requires the coexistence of two naturally occurring single nucleotide polymorphisms (snps) in combination; neither snp alone is sufficient. These data illustrate the importance of studying snps in combination, because the functional significance of a given snp may only be evident in a specific setting of additional snps in the same or different genes.     

Influence of interleukin-4 gene polymorphisms and interleukin-4 serum level on susceptibility and severity of rheumatoid arthritis in Egyptian population

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease in which interleukin-4 (IL-4) plays an important role. This study aimed to investigate the influence of IL-4 variable number of tandem repeats (VNTRs) and IL-4-590 promoter polymorphisms on RA susceptibility, activity and severity in Egyptian population.Materials and methodsOne hundred and seventy-two RA patients and 172 controls were enrolled in this study. IL-4 VNTR and IL-4-590 promoter polymorphisms were genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum IL-4 and anti-cyclic citrullinated peptides (anti-CCPs) antibody concentrations were measured by enzyme linked immunosorbent assay (ELISA).ResultsSubjects with IL-4-590 TT genotype were significantly more likely to develop RA. IL-4 VNTR 1/1 genotype, IL-4-590 TT and CT genotypes were significantly more associated with erosive RA and positive anti-CCP antibody. RA severity parameters were significantly increased, while, IL-4 level was significantly decreased in RA patients with IL-4 VNTR 1/1 and IL-4-590 TT genotypes. Only patients with IL-4-590 TT genotype showed a significant increase of all RA activity parameters.ConclusionIL-4 VNTR and IL-4-590 promoter polymorphisms may be helpful for assessing RA severity in Egyptian population. Moreover, IL-4-590 promoter polymorphism may be associated with increased risk and activity of RA.     

Genetic variants of the receptors for thromboxane A2 and IL-4 in atopic dermatitis

Thromboxane A2 (TXA2) is an arachidonate metabolite which is considered to relate to chronic inflammation in atopic diseases characterized by elevated immunoglobulin E productivity. The elevation of immunoglobulin E levels involves many molecules including interleukin-4 (IL-4) and interleukin-4 receptor alpha chain (IL-4R alpha). To assess whether genetic variants of TXA2 receptor, IL-4 and IL-4R alpha genes relate to the elevation of serum immunoglobulin E levels in patients with atopic dermatitis (AD), we conducted an association study of genetic polymorphisms of TXA2 receptor (795C/T), IL-4 (-589C/T), and IL-4R alpha (Ile50Val) in a Japanese population (n = 789). The TXA2 receptor 795TT genotype strongly related to AD with high serum immunoglobulin E concentrations. AD patients with both TXA2 receptor 795TT genotype and the IL-4R alpha Ile50/Ile50 genotype showed the greatest immunoglobulin E concentrations. These results suggest TXA2 receptor polymorphism strongly interacts with IL-4R alpha polymorphism as a major determinant of high serum immunoglobulin E levels in AD.     

Role of IL-4 Gene Polymorphisms in HBV-Related Hepatocellular Carcinoma in a Chinese Population

Background

Interleukin-4 (IL-4) is best known as an important mediator and modulator of immune and inflammatory responses. Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer, and genetic variations in the IL-4 gene may be associated with the risk of hepatitis B virus (HBV)-related HCC. However, few studies have been conducted on their association.

Objectives

To clarify the effects of IL-4 gene polymorphisms on the risk of HBV-related HCC, two common variants, −590C/T (rs2243250) and −33C/T (rs2070874), and their relationship with HBV-related disease risk were investigated in a Chinese population.

Methods

IL-4 −590C/T and −33C/T polymorphisms were examined in 154 patients with HBV-related HCC, 62 patients with HBV-induced liver cirrhosis (LC), 129 patients with chronic hepatitis B (CHB), and 94 healthy controls, using the polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing.

Results

Overall, no significant differences were observed regarding the IL-4 −590C/T and −33C/T polymorphism genotypes, alleles, or haplotypes between the patient groups and the healthy controls. However, the CC genotypes of IL-4 −590C/T and −33C/T polymorphisms were observed to be significantly associated with CHB in subgroup analysis in males [CC versus TT (OR: 4.193, 95% CI: 1.094–16.071, P = 0.037; and OR: 3.438, 95% CI: 1.032–11.458, P = 0.044) and CC versus TT+CT (OR: 4.09, 95% CI: 1.08–15.49, P = 0.038; and OR: 3.43, 95% CI: 1.04–11.28, P = 0.042)].

Conclusions

These findings suggest that genetic variants in IL-4 −590C/T and −33C/T polymorphisms may be a risk factor for CHB in Chinese males but not for HBV-related LC or HCC.     

Associations of IL-4, IL-4R, and IL-13 gene polymorphisms in coal workers' pneumoconiosis in China: a case-control study

Background

The IL-4, IL-4 receptor (IL4R), and IL-13 genes are crucial immune factors and may influence the course of various diseases. In the present study, we investigated the association between the potential functional polymorphisms in IL-4, IL-4R, and IL-13 and coal workers'' pneumoconiosis (CWP) risk in a Chinese population.

Methods

Six polymorphisms (C-590T in IL-4, Ile50Val, Ser478Pro, and Gln551Arg in IL-4R, C-1055T and Arg130Gln in IL-13) were genotyped and analyzed in a case-control study of 556 CWP and 541 control subjects.

Results

Our results revealed that the IL-4 CT/CC genotypes were associated with a significantly decreased risk of CWP (odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.58–0.95), compared with the TT genotype, particularly among subgroups of age <65 years (OR = 0.68, 95%CI = 0.46–0.99) and dust exposure years ≥26 years (OR = 0.69, 95%CI = 0.50–0.94). Moreover, the polymorphism was significantly associated with risk of CWP patients with stage I. In addition, a combined effect was observed in a dose-dependent manner with increasing numbers of risk variant alleles (P _trend = 0.023), and individuals with 11–12 risk alleles had a 47% higher risk of CWP than those with 0–8 risk alleles (OR = 1.47, 95% CI = 1.05–2.05).

Conclusions

Our results suggest that the IL-4 C-590T polymorphism is involved in the etiology of CWP and susceptibility to this disease. Larger studies are warranted to validate our findings.     

Interleukin-4 -590T/C polymorphism influences the susceptibility to nonsmall cell lung cancer

Lung cancer is the leading cause of cancer mortality worldwide. Nonsmall cell lung cancer (NSCLC) accounts for most of these cases. Interleukin 4 (IL-4) is a typical pleiotropic T helper 2 cytokine and plays crucial roles in tumor immunology. IL-4 gene -590T/C polymorphism has been shown to be associated with different autoimmune diseases and cancers. The present study evaluated the correlation between this polymorphism and the susceptibility to NSCLC in the Chinese population. The IL-4 variant -590T/C was detected by polymerase chain reaction-restriction fragment length polymorphism in 1072 NSCLC cases and 1126 age-matched healthy controls. Data were analyzed using the Chi-square test. Results showed that frequencies of IL-4 -590 TC, CC genotype, and -590 C allele were significantly lower in patients with NSCLC than in healthy controls (odds ratio [OR]=0.77, 95% confidence interval [CI] 0.64-0.93, p=0.006; OR=0.54, 95% CI 0.38-0.76, p=0.0004; and OR=0.72, 95% CI 0.62-0.83, p=1.1 × 10(-5), respectively). Our data suggest that the -590T/C polymorphism of the IL-4 gene is associated with a decreased susceptibility to NSCLC.     

The IL-8 gene polymorphisms and the risk of the hepatitis B virus/infected patients

Interleukin-8 (IL-8) belongs to the superfamily of CXC chemokines, contributing to human cancer progression through potential mitogenic, angiogenic, and motogenic functions. We hypothesize that the functional polymorphism of IL-8 may influence the inflammatory process during pathological stage from hepatitis to hepatocellular carcinoma (HCC). Two polymorphisms in the IL-8 gene (-251A/T and +781C/T) were examined in 160 cases of chronic hepatitis B, 80 cases of hepatitis B virus (HBV)-related liver cirrhosis (LC), 150 cases of HBV-related HCC, and 150 healthy controls using polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing. In the LC group, the AA genotypes were associated with a significantly decreased risk of LC compared with the TT genotype (OR=0.14, 95% CI 0.02-0.87, p=0.035). The data also revealed that subjects with the A allele appeared to have lower susceptibility to LC than those with the T allele (OR=0.48, 95% CI 0.25-0.92, p=0.027). The +781C/T polymorphism of IL-8 was not found relevant to the liver diseases. This study indicated that the IL-8 gene -251 AA genotype might be a protect factor for LC.     

Association between IL-4 polymorphism and acute rejection of solid organ allograft: A meta-analysis

Background

Cytokines have been implicated in the acute rejection of solid organ transplantation. Many studies have investigated the association between recipient or donor IL-4 polymorphism and acute rejection, with different studies reporting inconclusive results.

Methods

We searched PUBMED and EMBASE until June 2012 to identify eligible studies investigating the association between IL-4 polymorphism with acute rejection after solid organ transplantation. Statistical analysis was performed using STATA10.0.

Results

A total of 12 studies were included. Pooled ORs suggested 1) no significant association was detected between recipient or donor IL-4 − 590C/T polymorphism and acute rejection of solid allograft; 2) no significant association was detected between recipient IL-4 − 33C/T polymorphism and acute rejection of solid allograft; 3) when stratified by transplantation type, IL-4 − 590C/T polymorphism was associated with acute rejection of liver transplantation (T/T + C/T vs. C/C: OR = 0.36, 95%CI = 0.14–0.90); 4) significantly decreased risk of acute rejection was detected in recipient IL-4 − 590*T-negative/donor T-positive genotype pairs than all other recipient–donor IL-4 − 590T/C pairs (OR = 0.14, 95%CI = 0.03–0.66).

Conclusions

Our meta-analysis suggested that recipient IL-4 − 590C/T polymorphism was associated with acute rejection of liver transplantation, but nor renal or heart transplantation. It was also suggested that combined recipient IL-4 − 590*T-negative/donor T-positive genotype may suffer decreased risk of acute rejection of solid allograft. Further well-designed studies with larger sample size were required to verify our findings, with focus on the association of IL-4 polymorphism with acute rejection in patients with liver transplantation and studies investigating combined recipient–donor genotype.     

Association analysis of IL-4 VNTR polymorphism with rheumatoid arthritis in Iranian patients

Rheumatoid arthritis (RA) is an autoimmune disease characterized by movement disability and pain in the joints. The affected individuals are susceptible to other subsequent diseases, exacerbating the condition. To find out the genetic variability of this disease at the genomic level for the first time in the Iranian population, we carried out an investigation on the VNTR of IL-4 gene within its third intron. For this goal we isolated the genomic DNA from blood samples of 576 rheumatoid arthritis patients and 546 healthy controls and investigated the presence or absence of specific amplicons via polymerase chain reaction (PCR). The size of each amplicon on a 1.5% agarose gel corresponded to a certain number of tandem repeats which indicated a specific allele. Statistical test of χ² Fisher’s exact test and odds ratio (OR) was used to analyze the data. The results showed that RA1/RA1 genotype was the dominant genotype in both healthy controls and patients and the heterozygote genotype of RA1/RA2 was observed more in the healthy controls than patients (108 vs. 66) with significant difference with P value < 0.005 and odds ratio of 0.214. However two genotypes of RA2/RA2 and RA2/RA3 were exclusively observed in the patients’ samples with P value = 0.023 and odds ratio of 0.988. We concluded that IL-4 VNTR polymorphism has a strong association with rheumatoid arthritis and might be a high risk factor for development of rheumatoid arthritis in the investigated Iranian population.     

Analysis of polymorphism of the interleukin-4 gene of healthy and HIV-infected persons

The distribution of the allel variants of the promoter area (C = 590T) of the interleukin-4 (IL-4) gene in HIV-infected and relatively healthy representatives of the Caucasoid population has been studied. The relationship between the genotypes of this polymorphism and the production of IL-4 by mononuclear cells of peripheral blood as well as distribution of IL-4 genotypes among males and females is analyzed. The occurrence of the homozygous combination of the allel variant C/C of the promoter of IL-4 has been shown to prevail almost twofold over the occurrence of the variant C/T among healthy donors and HIV-infected patients. Sexual differences play an essential role in the character of inheriting the allel variants of the genes of IL-4, the presence of the homozygous variant C/C or T/T being a risk factor of HIV infection in males. As revealed in this study, in the peripheral blood of healthy donors mononuclear cells having genotype C/C differ from cells with the heterozygous variant C/T in higher spontaneous production of IL-4 and, simultaneously, in lower capacity for the activation of its production in response to stimulation with mitogen. In HIV-infected patients mononuclear cells differ in higher spontaneous production of IL-4 in comparison with controls. We may thus infer that the human genotype controlling the initial level of the production of IL-4 by lymphocytes Th2 may influence the intensity of antibody production in the process of infection.     

Association study on IL4, IL13 and IL4RA polymorphisms in mite-sensitized persistent allergic rhinitis in a Chinese population

Background

The IL4, IL13, and IL4 receptor α chain (IL4RA) genes are candidate genes for atopic diseases. We hypothesized that the polymorphisms in these genes are associated with persistent allergic rhinitis (PER).

Objective

To investigate the association of the potential functional polymorphisms in IL4, IL13, and IL4RA with PER induced by house dust mites in a Chinese population.

Methods

Using the TaqMan method, we genotyped six single nucleotide polymorphisms (SNPs) including C-590T in IL4, C-1055T and Arg130Gln in IL13, and Ile50Val, Ser478Pro and Gln551Arg in IL4RA, in a case-control study of 265 patients with PER and 275 healthy controls.

Results

We found that the CT/CC genotypes in IL4 C-590T were associated with a significantly decreased risk of mite-sensitized PER [adjusted odds ratio (OR)  = 0.64, 95% confidence interval (CI) 0.45–0.92], compared to the TT genotype. Furthermore, PER patients with CT/CC genotypes had significantly lower serum levels of total IgE than those with TT genotype (P = 0.001). However, there was no significant association of the IL13 and IL4RA polymorphisms with mite-sensitized PER (P>0.05).

Conclusions

Our results suggest that the C-590T polymorphism in IL4 may contribute to the susceptibility to mite-sensitized PER in a Chinese population.     

Investigation of relationship between IL-6 gene variants and hypertension in Turkish population

Hypertension (HT) is a common and life threating health problem worldwide leading to stroke, heart attack and renal failure. It is characterized by elevated blood pressure forced heart load. Human interleukin-6 (IL-6) and C- reactive protein (CRP) are known to be involved in inflammatory processes. IL-6 gene is a polymorphic gene which −174 G/C is a common and −572 G/C is a rare polymorphisms identified in promoter region. Publications on IL-6 gene polymorphisms raised the question whether this gene polymorphisms lead to susceptibility to HT or not. To investigate the effects of IL-6 gene −174 G/C (rs 1800795) and −572 G/C (rs1800796) polymorphisms on plasma IL-6 and CRP levels and their associations with hypertension disease in Turkish population we analyzed −174 G/C and −572 G/C polymorphisms and plasma IL-6 and CRP levels in 111 healthy controls and 108 hypertension patients from Adıyaman, Turkey. We determined the genotypes using polymerase chain reaction-restriction fragment length polymorphism and analyzed plasma levels of IL-6 by ELISA and CRP by automated standard biochemical methods. We have found no statistically significant differences between IL-6 gene −174 G/C and −572 G/C genotypes and allelic frequencies and IL-6 and CRP plasma levels and HT (p > 0.05). No CC genotype was found in control subjects for −572 G/C polymorphism. In conclusion, we found relation to −174 G/C and −572 G/C gene variants between neither IL-6 and CRP levels nor hypertension. The −572 G allele and GG genotype are predominant in Turkish population in Adıyaman, Turkey whereas the CC genotype is very rare.     

Association of polymorphisms in the human IL-10 and IL-18 genes with rheumatoid arthritis

The decrease of anti-inflammatory cytokine and increase of pro-inflammatory cytokine was observed in rheumatoid arthritis (RA). Interleukin-10 (IL-10), a potent anti-inflammatory cytokine, has been demonstrated to suppress joint swelling and deformation in RA animal model. Interleukin-18 (IL-18), a widely distributed pro-inflammatory cytokine, induces the production of IFN-γ, activate NK cells, and promote inflammation. Recent studies demonstrated that the serum IL-10 and IL-18 levels may be influenced by genetics and related to susceptibility to several autoimmune diseases. In the present study, using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and DNA sequencing techniques, we analyzed the genotype and allele distributions of two single nucleotide polymorphisms (SNP) loci in the promoter region of IL-10 and IL-18 genes (IL-10-592 A/C and IL-18-607 A/C loci, respectively). Our results indicated that IL-10-592 allelic and genotypic frequencies were significantly different between the RA patients and normal subjects (P < 0.05). In addition, significant differences of IL-10-592 allelic and genotypic frequencies were also detected between the patients with or without anti-cyclic citrullinated peptide antibody (anti-CCP) (P < 0.05). In contrast, allelic and genotypic frequencies of IL-18-607 did not show significant difference between RA patients and normal subjects (P > 0.05) or between anti-CCP-positive and anti-CCP-negative RA patients (P > 0.05). Furthermore, ELISA detection of IL-10 and IL-18 serum levels revealed that the genotype of IL-10-592 was associated with IL-10 serum level (P < 0.05), but the genotype and allele frequency of IL-18-607 was not associated with IL-18 serum level (P > 0.05). Taken together, our findings provide new insight for the polymorphism of IL-10 gene in the pathogenesis of RA.     

Association of immune system gene polymorphisms with quantitative features which are pathogenetically important in chronic viral hepatitis

Association study was performed for genetic polymorphisms IL4 C(-590)T, IL4RA Ile50Val, TNF G(-308)A, to estimate their effect on quantitative features which are pathogenetically important for chronic viral hepatitis course, i.e. levels of IL4, IL10, IL12, tumor necrosis factor alpha, fibronectin, collagenase, protease inhibitors, macroglobulines, elastases, free and protein-bound hydroxyproline. It has been shown that A allele of TNF G(-308)A polymorphism is associated with decreased TNF-alpha, increased IL4 and IL12, as well as with low level of protein-bound hydroxyproline. In addition, association of CT genotype of IL4 C(-590)T polymorphism and high level of protein-bound hydroxyproline has been identified.     

TGF-beta1 and IL-6 gene polymorphism in Spanish brucellosis patients

Polymorphisms in the cytokine genes have allowed for the understanding of the genetic determinants in several diseases. We investigated the polymorphism of the transforming growth factor (TGF)-beta1 and IL-6 genes in relation to susceptibility to human brucellosis. We typed 82 Spanish brucellosis patients and 102 healthy controls for TGF-beta1 polymorphisms in codons 10 and 25, and IL-6 promoter polymorphism at position -174 by PCR-SSP methods. The T/T G/G genotype of the TGF-beta1 gene was significantly increased in patients compared to controls (49% vs. 32%) P=0.02; OR=1.99 (1.05-3.80) and the T/C G/G genotype was significantly less common in the patients compared to the controls (32% vs. 49%) P=0.01; OR=0.48 (0.25-0.92). The CC genotype of codon 10 was significantly increased in the patients who had focal forms of the disease as compared with those who did not develop focal forms (19% vs. 4%), P=0.03; OR=0.19 (0.02-1.10). No differences were found in the IL-6 variants between the patients and the controls. These results suggest that polymorphism of the TGF-beta1 gene may be involved in susceptibility to brucellosis and to developing focal forms of the disease in a group of patients from southern Spain.     

Associations between the IL-4 -590 T allele and Plasmodium falciparum infection prevalence in asymptomatic Fulani of Mali

In this study, we compared the genotype and allele frequencies of the IL-10 -1087 A/G and IL-4 -590 C/T single nucleotide polymorphisms in asymptomatic subjects of two sympatric ethnic tribes differing in susceptibility to malaria, the Fulani and the Dogon in Mali. The genotype data was correlated with ethnicity and malariometric indexes. A statistically significant inter-ethnic difference in allele and genotype frequency for both loci was noted (P<0.0001). Within the Fulani, the prevalence of Plasmodium falciparum infection, as detected by both microscopy and PCR, was associated with the IL-4 -590 T allele (P=0.005 and P=0.0005, respectively), whereas, no such associations were seen in the Dogon. Inter-ethnic differences in spleen rates, higher in the Fulani than the Dogon, were seen between T carriers (TT and CT) of both groups (P<0.0001). Parasite densities and number of concurrent clones did not vary between IL-4 genotypes within any of the studied groups. These results suggest an association between the IL-4 -590 T allele and P. falciparum prevalence within the Fulani but not the Dogon. No associations between IL-10 genotypes and studied malariometric indexes were observed in any of the two communities.     

Effects of common atopy-associated amino acid substitutions in the IL-4 receptor alpha chain on IL-4 induced phenotypes

The human IL-4 receptor alpha chain gene (IL4R) is highly polymorphic and controversial reports have been published with respect to the association of different single nucleotide polymorphisms (SNPs) with atopy markers. Here we analyzed the functional and associational relevance of common IL4R coding SNPs. Transfection of B cell lines expressing the IL-4R variant V75+R576 did not result in enhanced IL-4 induced CD23 expression compared to cell lines expressing the wild type IL-4R alpha chain. Transfection of the IL-4R variant P503 into a murine T cell line did not influence IL-4 induced T-cell proliferation compared to wild type constructs. Analysis of six IL4R coding SNPs (I75V, E400A, C431R, S436L, S503P, Q576R) and common haplotypes (frequency 0.05%) in blood donors (n=300) did not indicate a significant association with elevated serum IgE level. Moreover, the most informative IL4R coding SNPs (I75V, C431R, Q576R) and related two- and three-point haplotypes (frequency 0.05%) were analyzed in a second, extended group of blood donors (n=689). Again, no significant association with elevated serum IgE was detectable. We conclude that common coding SNPs in the IL4R gene are unlikely to contribute significantly to increased IgE levels and variations outside the coding region may influence atopy susceptibility.     

The lL-8 and IL-13 gene polymorphisms in inflammatory bowel disease and colorectal cancer

Inflammatory bowel diseases (IBD) and colorectal cancer (CRC) are disorders that originate from immune disturbances. In our study, we evaluated the association between the -251 T/A interleukin (IL)-8 and the -1112 C/T IL-13 polymorphisms, the risk of IBD, and CRC development. Genotypes were determined by PCR-restriction fragment length polymorphism in 191 patients with CRC, 150 subjects with IBD, and 205 healthy controls. We found an association between CRC and the presence of the -251 TA genotype and A allele of the IL-8 gene (odds ratios [ORs] 2.28 and 1.65). A similar relationship was observed between these polymorphic variants and ulcerative colitis (OR 2.05 for the -251 TA genotype and OR 1.47 for the -251 A allele) as well as Crohn's disease (ORs 3.11 and 1.56, respectively). Our research also revealed that the CT and TT genotypes of the IL-13 -1112 C/T polymorphism may be connected with a higher risk of CRC (ORs 2.28 and 1.65). The same genotypes affected the susceptibility of IBD (ORs 2.26 and 3.72). Our data showed that the IL-8 -251 T/A and IL-13 -1112 C/T polymorphisms might be associated with the IBD and CRC occurrence and might be used as predictive factors of these diseases in a Polish population.