Single nucleotide polymorphisms of the genes encoding IL-10 and TGF-Beta1 in Iranian children with atopic dermatitis

Background: Atopic dermatitis is an inflammatory skin disease in which both genetic and environmental factors interact to determine the susceptibility and severity of the disease. Objective: The aim of this study was to determine the association between atopic dermatitis and IL-10 and TGF-Beta1 gene polymorphisms. Methods: The allele and genotype frequencies of genes encoding for IL-10 and TGF-Beta1 were investigated in 89 patients with atopic dermatitis in comparison with 138 in the control group using the PCR-SSP method. Results: A significant increase was found in the frequency of the TGF-Beta1 codon 10/C allele among patients (p < 0.001, OR = 6.77), whereas a significant decrease was observed in the frequency of the T allele at the same position (p < 0.001, OR = 0.14). The frequency of the TGF-Beta1 codon 25/G allele in the control group was significantly higher than among patients (p < 0.001, OR = 0.08). A significant positive correlation was seen between CC (p < 0.001, OR = 15.10) and CG (p < 0.001) genotypes and AD at codons 10 and 25, respectively. The most frequent haplotypes among patients was TGF-Beta1 CG which was significantly higher than in the control subjects (50% in patients vs. 39.9% in controls, p = 0.042). A significant increase was found in the frequency of TGF-Beta CC (36% in patients vs. 7.6% in controls, p < 0.001) and TC (14% in patients vs. 0% in controls, p < 0.001) haplotypes among patients compared to controls. By contrast, the TGF-Beta1 TG haplotype was significantly lower in patients than controls (0% in patients vs. 52.5% in controls, p < 0.001). There were no significant differences in the frequency of alleles, genotypes and haplotypes of the IL-10 gene. Conclusions: We found a strong association between the polymorphisms of the TGF-Beta1 gene at codon 10 and codon 25 positions and atopic dermatitis (AU)

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Single nucleotide polymorphisms of the genes encoding IL-10 and TGF-ß1 in Iranian children with atopic dermatitis.

BACKGROUND: Atopic dermatitis is an inflammatory skin disease in which both genetic and environmental factors interact to determine the susceptibility and severity of the disease. OBJECTIVE: The aim of this study was to determine the association between atopic dermatitis and IL-10 and TGF-ß1 gene polymorphisms. METHODS: The allele and genotype frequencies of genes encoding for IL-10 and TGF-ß1 were investigated in 89 patients with atopic dermatitis in comparison with 138 in the control group using the PCR-SSP method. RESULTS: A significant increase was found in the frequency of the TGF-ß1 codon 10/C allele among patients (p<0.001, OR=6.77), whereas a significant decrease was observed in the frequency of the T allele at the same position (p<0.001, OR=0.14). The frequency of the TGF-ß1 codon 25/G allele in the control group was significantly higher than among patients (p<0.001, OR=0.08). A significant positive correlation was seen between CC (p<0.001, OR=15.10) and CG (p<0.001) genotypes and AD at codons 10 and 25, respectively. The most frequent haplotypes among patients was TGF-ß1 CG which was significantly higher than in the control subjects (50% in patients vs. 39.9% in controls, p=0.042). A significant increase was found in the frequency of TGF-ß CC (36% in patients vs. 7.6% in controls, p<0.001) and TC (14% in patients vs. 0% in controls, p<0.001) haplotypes among patients compared to controls. By contrast, the TGF-ß1 TG haplotype was significantly lower in patients than controls (0% in patients vs. 52.5% in controls, p<0.001). There were no significant differences in the frequency of alleles, genotypes and haplotypes of the IL-10 gene. CONCLUSIONS: We found a strong association between the polymorphisms of the TGF-ß1 gene at codon 10 and codon 25 positions and atopic dermatitis.

Association of interleukin 1 gene cluster and interleukin 1 receptor gene polymorphisms with ischemic heart failure.

BACKGROUND: Proinflammatory cytokines have been known to play a considerable part in the pathomechanisms of chronic heart failure (CHF). Given the importance of proinflammatory cytokines in the context of the failing heart, we assessed whether the polymorphisms of interleukin (IL)-1 gene cluster, including IL-1α, IL-1ß, and IL-1 receptor antagonist (IL-1RA) and IL-1R gene are predictors of CHF due to ischemic heart disease. METHODS: Forty- three patients with ischemic heart failure were recruited in this study as patients group and compared with 140 healthy unrelated control subjects. Using polymerase chain reaction with sequence-specific primers method, the allele and genotype frequency of 5 single nucleotide polymorphisms (SNPs) within the IL-1α (-889), IL-1ß (-511, +3962), IL-1R (psti 1970), and IL-1RA (mspa1 11100) genes were determined. RESULTS: The frequency of the IL-1ß -511/C allele was significantly higher in the patient group compared to that in the control group (p = 0.031). The IL-1ß (-511) C/C genotype was significantly overrepresented in patients compared to controls (p = 0.022). CONCLUSIONS: Particular allele and genotype in IL-1ß gene were overrepresented in patients with ischemic heart failure, possibly affecting the individual susceptibility to this disease (Tab. 1, Ref. 27).

FLG single nucleotide polymorphisms in chronic idiopathic urticaria

BACKGROUND: Filaggrin (FLG), which is formed from profilaggrin protein during epidermal terminal differentiation, is a prerequisite to squame biogenesis and thus for perfect formation of the skin barrier. Yet, the relationship between genetic polymorphisms of FLG and chronic idiopathic urticaria (CIU) has not been investigated. METHODS: The study population consisted of 93 CIU patients and 93 healthy control subjects without a history of allergic, autoimmune or any other systemic disease. Five single nucleotide polymorphisms (SNPs) of FLG were investigated: rs2485518, rs3126065, rs2786680, rs3814300, and rs3814299. RESULTS: For all the investigated polymorphisms, 100% of both CIU patients and control subjects exhibited one given allele and consequently one given genotype as following: A/A genotype for two SNPs, rs3126065 and rs2786680, C/C genotype for two SNPs, rs2485518 and rs3814300, and G/G genotype for one SNP rs3814299 of FLG, and hence no association was found between either allele frequencies or genotype distributions of FLG SNPs and CIU in an Iranian population. CONCLUSIONS: The present study examined the possible relationship between SNPs of FLG and CIU for the first time, and demonstrated that none of five investigated SNPs (rs2485518, rs3126065, rs2786680, rs3814300, and rs3814299) are correlated with CIU in an Iranian population. Further investigations are required to address whether ethnicity/race impacts on relationship between SNPs of FLG and CIU

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Gene polymorphisms of interleukin-10 and transforming growth factor beta in allergic rhinitis

BACKGROUND: Allergic rhinitis (AR) is a polygenic inflammatory disorder of the upper respiratory airway with an increasing prevalence worldwide. Interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β), as two cytokines with pleiotropic effects on both innate and adaptive immunity, play important roles in allergic responses. Therefore, this study was performed to evaluate the associations of five polymorphisms of IL-10 and TGF-β genes with AR. MATERIALS AND METHODS: Ninety-eight patients with AR along with 140 healthy volunteers with no history of AR and with the same ethnicity of the patients were recruited in this study. Genotyping was done for three polymorphisms in promoter region of IL-10 gene (rs1800896, rs1800871, rs1800872), and two polymorphisms in the exonic region of TGF-β1 gene (rs1982037, rs1800471) using PCR sequence-specific-primers method. RESULTS: A allele and AA genotype in rs1800896 of IL-10 and TT genotype in rs1982037 in TGF-β were significantly less frequent in the patients than in controls. While the C allele and the CG genotype in rs1800471 in TGF-β1 were associated with a higher susceptibility to AR. C/C and T/C haplotypes (rs1982037, rs1800471) in TGF-β1 gene and A/C/A, A/T/C and G/C/A haplotypes (rs1800896, rs1800871, rs1800872) in IL-10 gene were found with higher frequencies in patients than controls. Patients with CC genotype in rs1800871 in Il-10 had significantly lower levels of IgE. CONCLUSION: We found that certain genetic variants in IL-10 and TGF-β polymorphisms were associated with susceptibility to AR as well as some clinical parameters in the patients with AR

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FLG single nucleotide polymorphisms in chronic idiopathic urticaria.

BACKGROUND: Filaggrin (FLG), which is formed from profilaggrin protein during epidermal terminal differentiation, is a prerequisite to squame biogenesis and thus for perfect formation of the skin barrier. Yet, the relationship between genetic polymorphisms of FLG and chronic idiopathic urticaria (CIU) has not been investigated. METHODS: The study population consisted of 93 CIU patients and 93 healthy control subjects without a history of allergic, autoimmune or any other systemic disease. Five single nucleotide polymorphisms (SNPs) of FLG were investigated: rs2485518, rs3126065, rs2786680, rs3814300, and rs3814299. RESULTS: For all the investigated polymorphisms, 100% of both CIU patients and control subjects exhibited one given allele and consequently one given genotype as following: A/A genotype for two SNPs, rs3126065 and rs2786680, C/C genotype for two SNPs, rs2485518 and rs3814300, and G/G genotype for one SNP rs3814299 of FLG, and hence no association was found between either allele frequencies or genotype distributions of FLG SNPs and CIU in an Iranian population. CONCLUSIONS: The present study examined the possible relationship between SNPs of FLG and CIU for the first time, and demonstrated that none of five investigated SNPs (rs2485518, rs3126065, rs2786680, rs3814300, and rs3814299) are correlated with CIU in an Iranian population. Further investigations are required to address whether ethnicity/race impacts on relationship between SNPs of FLG and CIU.

Gene polymorphisms of interleukin-10 and transforming growth factor beta in allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a polygenic inflammatory disorder of the upper respiratory airway with an increasing prevalence worldwide. Interleukin-10 (IL-10) and transforming growth factor-beta (TGF-ß), as two cytokines with pleiotropic effects on both innate and adaptive immunity, play important roles in allergic responses. Therefore, this study was performed to evaluate the associations of five polymorphisms of IL-10 and TGF-ß genes with AR. MATERIALS AND METHODS: Ninety-eight patients with AR along with 140 healthy volunteers with no history of AR and with the same ethnicity of the patients were recruited in this study. Genotyping was done for three polymorphisms in promoter region of IL-10 gene (rs1800896, rs1800871, rs1800872), and two polymorphisms in the exonic region of TGF-ß1 gene (rs1982037, rs1800471) using PCR sequence-specific-primers method. RESULTS: A allele and AA genotype in rs1800896 of IL-10 and TT genotype in rs1982037 in TGF-ß were significantly less frequent in the patients than in controls. While the C allele and the CG genotype in rs1800471 in TGF-ß1 were associated with a higher susceptibility to AR. C/C and T/C haplotypes (rs1982037, rs1800471) in TGF-ß1 gene and A/C/A, A/T/C and G/C/A haplotypes (rs1800896, rs1800871, rs1800872) in IL-10 gene were found with higher frequencies in patients than controls. Patients with CC genotype in rs1800871 in Il-10 had significantly lower levels of IgE. CONCLUSION: We found that certain genetic variants in IL-10 and TGF-ß polymorphisms were associated with susceptibility to AR as well as some clinical parameters in the patients with AR.

Association study of interleukin-1 family and interleukin-6 gene single nucleotide polymorphisms in recurrent aphthous stomatitis.

Recurrent aphthous stomatitis (RAS) is a common painful, ulcerative oral inflammatory disorder with unknown aetiology. Immune system and aberrant cytokine cascade deemed to be critical in outbreaks of RAS ulcers. Interleukin-1 (IL-1) and IL-6 are the most potent pro-inflammatory cytokines. Single nucleotide polymorphisms (SNPs) of IL-1 and IL-6 genes can affect the secretion of these cytokines. The aim of this study was to investigate the association between RAS and IL-6 and IL-1 in Iranian subjects with minor RAS. Genomic DNA was obtained from 64 Iranian patients with RAS. IL-1α C -889 T, IL-1ß C -511 T, IL-1ß C +3962 T, IL-1R C pst-I 1970 T, IL-1Ra C Mspa-I11100 T, IL-6 C -174 G and IL-6 A nt +565 G polymorphisms were determined using polymerase chain reaction with sequence-specific primers (PCR-SSP). The frequency of C -174 C genotype in the patients group was significantly different from the healthy control. No other significant differences were found in genotype and alleles frequencies between the two groups. These results indicate that certain SNPs of IL-6 gene at position -174 which located in promoter have association with predisposition of individuals to RAS.

RAD50 single-nucleotide polymorphism in predominantly antibody deficiency

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AICDA single nucleotide polymorphism in common variable immunodeficiency and selective IgA deficiency

BACKGROUND: Primary antibody deficiencies (PADs) are a heterogeneous group of disorders, characterised by increased susceptibility to recurrent bacterial infections. Common variable immunodeficiency (CVID) is the most important PAD from the clinical point of view and selective IgA deficiency (IgAD) is the most common PAD. However, the underlying gene defect in both is still unknown. As a recent study in Europe showed an association between a single nucleotide polymorphism (SNP) of AICDA gene with PADs, this study was performed to evaluate such an association in Iranian patients. METHODS: Fifty-eight patients with PAD, including 39 CVID and 19 IgAD, as well as 34 healthy volunteers, were enrolled in this study. Genotyping was done in all groups for an intronic SNP in AICDA (rs2580874), using real-time PCR genotyping assay. RESULTS: The less frequent genotype of AICDA in IgAD patients was AA, seen in 10.5% of the patients, which was much lower than the 30.8% in CVID patients and 38.2% in the controls. However, these differences were not significant. Indeed the GG genotype in the patients with PADs was seen in 20.7%, compared to 8.8% in the controls without any significant difference. CONCLUSIONS: There was no significant association between the previously reported genetic variant of AICDA gene and the development of CVID or IgAD, but further multi-center studies are also needed

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Association of single nucleotide polymorphisms of interleukin-1 family with atopic dermatitis

BACKGROUND: Interleukin-1 (IL-1) seems to have an important role in early reactions towards microbes, while its genetic variability could affect this role in atopic patients who have a distressed immunity towards dermatological infections. METHODS: Eighty-nine patients with atopic dermatitis (AD), who were referred to a main referral paediatric hospital, were enrolled in this study. Single nucleotide polymorphisms (SNP) of the following IL-1 cluster genes were assessed in this group of patients: IL-1α −889, IL-1β −511, IL-1β +3962, IL-1R Pst-I 1970, and IL-1RA Mspa-I 11100. The results were compared with a group of 140 healthy subjects from the same region. RESULTS: Fourteen percent of the controls had TT homozygous genotype in IL-1R at position Pst-I 1970, while only 2% of the patients with AD had this genotype (p = 0.005, OR: 0.14, 95%CI: 0.02-0.64). The CC homozygous genotype was the most common genotype in IL-1α position −889 and IL-1β at position +3962 in both groups of patients with AD and the controls, while the TC heterozygous genotype was the most common genotype in IL-1β at position −511 and IL-1R at position Pst-I 1970, with no significant difference between the two groups. CONCLUSIONS: This study showed a significant negative association in the IL-1R Mspa-I 11100 TT homozygous genotype in the patients with AD

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Association of single nucleotide polymorphisms of interleukin-1 family with atopic dermatitis.

BACKGROUND: Interleukin-1 (IL-1) seems to have an important role in early reactions towards microbes, while its genetic variability could affect this role in atopic patients who have a distressed immunity towards dermatological infections. METHODS: Eighty-nine patients with atopic dermatitis (AD), who were referred to a main referral paediatric hospital, were enrolled in this study. Single nucleotide polymorphisms (SNP) of the following IL-1 cluster genes were assessed in this group of patients: IL-1α -889, IL-1ß -511, IL-1ß +3962, IL-1R Pst-I 1970, and IL-1RA Mspa-I 11100. The results were compared with a group of 140 healthy subjects from the same region. RESULTS: Fourteen percent of the controls had TT homozygous genotype in IL-1R at position Pst-I 1970, while only 2% of the patients with AD had this genotype (p=0.005, OR: 0.14, 95%CI: 0.02-0.64). The CC homozygous genotype was the most common genotype in IL-1α position -889 and IL-1ß at position +3962 in both groups of patients with AD and the controls, while the TC heterozygous genotype was the most common genotype in IL-1ß at position -511 and IL-1R at position Pst-I 1970, with no significant difference between the two groups. CONCLUSIONS: This study showed a significant negative association in the IL-1R Mspa-I 11100 TT homozygous genotype in the patients with AD.

AICDA single nucleotide polymorphism in common variable immunodeficiency and selective IgA deficiency.

BACKGROUND: Primary antibody deficiencies (PADs) are a heterogeneous group of disorders, characterised by increased susceptibility to recurrent bacterial infections. Common variable immunodeficiency (CVID) is the most important PAD from the clinical point of view and selective IgA deficiency (IgAD) is the most common PAD. However, the underlying gene defect in both is still unknown. As a recent study in Europe showed an association between a single nucleotide polymorphism (SNP) of AICDA gene with PADs, this study was performed to evaluate such an association in Iranian patients. METHODS: Fifty-eight patients with PAD, including 39 CVID and 19 IgAD, as well as 34 healthy volunteers, were enrolled in this study. Genotyping was done in all groups for an intronic SNP in AICDA (rs2580874), using real-time PCR genotyping assay. RESULTS: The less frequent genotype of AICDA in IgAD patients was AA, seen in 10.5% of the patients, which was much lower than the 30.8% in CVID patients and 38.2% in the controls. However, these differences were not significant. Indeed the GG genotype in the patients with PADs was seen in 20.7%, compared to 8.8% in the controls without any significant difference. CONCLUSIONS: There was no significant association between the previously reported genetic variant of AICDA gene and the development of CVID or IgAD, but further multi-center studies are also needed.

Single-Nucleotide Polymorphisms of TNFA and IL1 in Allergic Rhinitis

Background: Allergic rhinitis is a complex polygenic disorder of the upper respiratory tract. Given that proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin (IL) 1 seem to play a role in the development of allergic rhinitis, we evaluated the associations between various single-nucleotide polymorphisms (SNPs) of the TNF and IL1 genes in a case-control study. Methods: The study population comprised 98 patients with allergic rhinitis. Genotyping was performed using polymerase chain reaction with sequence-specific primers for 2 TNFA promoter variants (rs1800629 and rs361525), 1 variant in the promoter region of IL1A (rs1800587), 2 SNPs in the IL1B gene (rs16944 and rs1143634), 1 variant in the IL1 receptor (rs2234650), and 1 in IL1RA (rs315952). Results: Patients who were homozygous for the T allele of rs16944 in IL1B had an 8.1-fold greater risk of allergic rhinitis than those with the C allele. In TNFA, a significant relationship was also detected between rs1800629 and rs361525 and allergic rhinitis. Except for rs1800587 in IL1A and rs315952 in IL1RA, significant differences were found between the patient and control groups for all other SNPs. Conclusions: We found that allelic variants in the TNFA and IL1 genes were not only associated with the risk of developing allergic rhinitis, but also affected disease course and severity (AU)

Antecedentes: La rinitis alérgica es una alteración poligénica compleja de las vías respiratorias. El TNF y la familia de la IL-1, como citoquinas proinflamatorias, parecen jugar un papel en el desarrollo de la rinitis alérgica. En este estudio de casos y controles, se evalúan las posibles asociaciones de diferentes polimorfismos de nucleótidos simples (SNPs) de los genes que regulan TNF- α e IL1. Métodos: Se estudiaron 19 pacientes con rinitis alérgica, los cuales fueron genotipados mediante PCR para primeras especie-específicos, para dos variantes del promotor del TNF- α (rs1800629 y rs361525), uno en el receptor de IL1 (rs2234650), dos SNPs en el gen de IL1ß (rs16944 y rs1143634), uno en el receptor de IL1 receptor (rs2234650) y IL1RA (rs315952). Resultados: En cuanto a los resultados obtenidos, los pacientes homicigotos para el alelo T de rs16944 en IL1ß mostraron un riesgo 8.1 veces mayor de tener rinitis alérgica que los que presentaban el alelo C. Con respecto al TNF- α, se observó una relación significativa entre los dos SNPs rs1800629 y rs361525 con la presentación de una rinitis alérgica. Excepto rs1800587, en IL1 α, y rs315952 en IL1RA, encuentran una diferencia significativa entre el grupo control y el de pacientes para el resto de los SNPs. Algunos SNPs se asociaron con el curso y con la gravedad de la enfermedad. Conclusiones: En conclusión, encontramos variantes genéticas de TNF-α y IL1 que se asocian con el riesgo de desarrollar una rinitis alérgica, y que también afectan al curso y gravedad de la enfermedad (AU)

Association between the interleukin 6 genotype at position -174 and atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic skin disorder of unknown origin that usually manifests for the first time in early infancy. Different types of genetic predisposition and environmental factors seem to be associated with the disease. METHODS: This study was performed to evaluate the frequency of alleles, genotypes, and haplotypes of interleukin (IL) 6 single-nucleotide polymorphisms (SNPs) at positions -174 and nt565 in 89 Iranian children with AD and 139 healthy controls. RESULTS: The G allele was significantly more frequent at position -174 in IL6 in atopic patients than in the healthy controls (P < .001; OR, 2.82). Genotype GG was found at the same position in 71% of the patients; this frequency was significantly higher than the frequency of 30% recorded in the controls (P < .001; OR, 5.60). The GG haplotype of IL6 (-174, nt565) was significantly more frequent in the atopic patients than in the healthy controls (P < .001; OR, 2.99). CONCLUSIONS: A significant increase in the frequency of the G allele and GG genotype at position -174 of IL6 was found in patients with AD, thus suggesting that production of this cytokine is greater in atopic patients.

Association Between the Interleukin 6 Genotype at Position –174 and Atopic Dermatitis

Antecedentes: La dermatitis atópica (DA) es una alteración crónica de la piel de origen desconocido, que habitualmente comienza en la infancia. Diferentes predisposiciones y factores ambientales se asocian a esta enfermedad. Métodos: Este estudio se realizó en 89 niños iraníes con DA para evaluar la frecuencia de alelos, genotipos y haplotipos de polimorfismos genéticos simples (SNPs) de la IL6 en las posiciones 174 y nt565 en comparación con 139 controles sanos. Resultados: Observamos un incremento significativo del alelo G de la IL6 en la posición –174 en los pacientes con DA comparado con el grupo control (p<0.001, OR=2.82). El genotipo GG de la misma posición se encontró en el 71% de los pacientes frente al 30% en los controles (p<0.001, OR=5.60). También se observa un incremento significativo en el haplotipo GG de la IL6 (-174, nt565) en los pacientes con DA comparados con los controles sanos (p<0.001, OR=2.99). Conclusiones: En conclusión observamos un aumento significativo del alelo Gallele y del genotipo GG en la posición -174 de la IL6 en pacientes con DA, lo que podría sugerir un aumento de la producción de esta citocina en los pacientes con DA (AU)

Background: Atopic dermatitis (AD) is a chronic skin disorder of unknown origin that usually manifests for the first time in early infancy. Different types of genetic predisposition and environmental factors seem to be associated with the disease. Methods: This study was performed to evaluate the frequency of alleles, genotypes, and haplotypes of interleukin (IL) 6 single-nucleotide polymorphisms (SNPs) at positions –174 and nt565 in 89 Iranian children with AD and 139 healthy controls. Results: The G allele was significantly more frequent at position –174 in IL6 in atopic patients than in the healthy controls (P<.001; OR, 2.82). Genotype GG was found at the same position in 71% of the patients; this frequency was significantly higher than the frequency of 30% recorded in the controls (P<.001; OR, 5.60). The GG haplotype of IL6 (–174, nt565) was significantly more frequent in the atopic patients than in the healthy controls (P<.001; OR, 2.99). Conclusions: A significant increase in the frequency of the G allele and GG genotype at position –174 of IL6 was found in patients with AD, thus suggesting that production of this cytokine is greater in atopic patients (AU)

A Novel CD40 Ligand Mutation in a Patient With Pneumonia, Neutropenia, and Hyperimmunoglobulin M Phenotype

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