Eotaxin gene single nucleotide polymorphisms in the promoter and exon regions are not associated with susceptibility to atopic dermatitis,but two of them in the promoter region are associated with serum IgE levels in patients with atopic dermatitis

Eotaxin is believed to play an important role in atopic dermatitis (AD) as a potent chemoattractant and activator of eosinophils and Th2 lymphocytes. The eotaxin gene is located at chromosome 17q21.1-q21.2, and linkage findings of AD on chromosome 17 were reported. Recently we have identified single nucleotide polymorphisms (SNPs) of eotaxin gene (-426C > T, -384A > G, 67G > A). To learn whether eotaxin gene SNPs are associated with susceptibility to AD or phenotypes of AD, we investigated the genotype frequencies at each SNP of the gene in AD patients and in controls. We examined 140 Japanese AD patients and 140 healthy Japanese individuals. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. No significant difference was observed in allele or genotype frequencies of any SNP between AD patients and controls. Serum immunoglobulin E (IgE) levels were significantly lower in CT and TT genotype than in CC (P = 0.038) in -426C > T SNP, and lower in GG than in AA and AG with borderline significance (P = 0.053) in -384A > G SNP in AD patients. Eotaxin gene SNPs in the promoter and exon regions are not associated with susceptibility to AD, but two of them in the promoter region are associated with phenotype of AD.     

Lack of association of CCR4 single nucleotide polymorphism with atopic dermatitis in Japanese patients

CCR4, a member of the CC chemokine receptor family, is believed to play an important role in the pathogenesis of atopic dermatitis. To examine whether CCR4 single nucleotide polymorphism (SNP) is associated with susceptibility to atopic dermatitis, we investigated the allele and genotype frequencies of C1014T SNP of CCR4 in 198 Japanese patients with atopic dermatitis and controls by a PCR-restriction fragment length polymorphism method. There was no significant difference in allele or genotype frequencies between patients with atopic dermatitis and controls. Serum IgE levels and peripheral blood eosinophil counts were not significantly different among genotypes. There was also no significant difference in allele or genotype frequencies between the patient subgroup with and without asthma, with mild or moderate disease, with and without family history of atopic dermatitis, or with and without family history of atopic disorders. C1014T SNP of CCR4 does not appear to be associated with susceptibility to atopic dermatitis in Japanese patients.     

Association of SPINK5 gene polymorphisms with atopic dermatitis in Northeast China

Background Defect in the SPINK5 gene is known to be implicated in Netherton syndrome (NS), and has been suggested to be a locus predisposing to atopy in general. Coding polymorphisms in SPINK5 exons 13, 14 and 26 have been reported to be associated with atopic dermatitis (AD), asthma and high level of IgE. Objectives To examine whether the SPINK5 gene polymorphisms are associated with AD in Northeast China, and to assess how variants influence selected phenotypic traits. Methods A case–control study was conducted on four non‐synonymous polymorphisms in the coding region of SPINK5 in AD and controls. The SPINK5 gene polymorphisms were analyzed using the PCR and RFLP methods. Results For the four non‐synonymous SNPs, A1103G(Asn368Ser), G1156A(Asp386Asn), G1258A(Glu420Lys), G2475T(Glu825Asp) in SPINK5, the allelic frequencies in the AD cohort were 0.55 for 1103G, 0.57 for 1156A, 0.54for 1258A, 0.62 for 2475T, consistent with those already published in the original British and Japanese cohorts. The T allele of SNP 2475G > T was found to be significantly associated with AD. There were significant differences in genotype frequencies for G1258A(Glu420Lys) and G2475T(Glu825Asp) but not for A1103G(Asn368Ser) and G1156A(Asp386Asn). Genotypes GA(420Glu/Lys), TT (2475Asp/Asp) and GT(2475Glu/Asp) were significantly more frequent in AD. However, the SPINK5 gene polymorphisms was found not to be associated with AD in regard to either serum IgE levels, concurrent allergic asthma or early onset of AD. Conclusions Our study confirms the association between SPINK5 and AD.     

Investigation of the eotaxin gene -426C-->T, -384A-->G and 67G-->a single-nucleotide polymorphisms and atopic dermatitis in Italian children using family-based association methods.

BACKGROUND: Eotaxin plays an important role in atopic dermatitis (AD) as a potent chemoattractant and activator of eosinophils and T-helper 2 lymphocytes. AIM: To investigate whether single-nucleotide polymorphisms of the eotaxin gene are associated with AD, we investigated the genotype and allelic frequencies of -426C-->T, -384A-->G, and 67G-->A SNPs in 130 Italian families. METHODS: In total, 130 children with either the extrinsic allergic or intrinsic nonallergic forms of AD (EAD and IAD) were recruited from 130 families. Genotyping was performed using PCR and restriction fragment length polymorphism analysis. RESULTS: A significant difference was observed in the genotype frequency of the -426C-->T SNP between children with EAD and those with IAD (P = 0.01), and between children with EAD and controls (P = 0.01). The allele frequencies of the -426C-->T SNP were significantly different between children with EAD and those with IAD (P < 0.01), and between children with EAD and controls (P < 0.01). For children with EAD, the genotype frequency of the -426C-->T SNP was no different between the groups with mild, moderate and severe SCORAD (P = NS). No significant association was observed between the -384A-->G and 67G-->A SNPs and the two groups of children with EAD and IAD compared with the control group. In 32 trios selected from 68 EAD families, the transmission disequilibrium test showed a preferential transmission of the -426T allele from the parents to affected offspring (P < 0.01). CONCLUSIONS: Our results suggest that in our group of children with AD, the eotaxin gene may play a crucial role in the development of extrinsic AD, probably with other genetic factors.     

The -431C>T polymorphism of thymus and activation-regulated chemokine increases the promoter activity but is not associated with susceptibility to atopic dermatitis in Japanese patients

BACKGROUND: Thymus and activation-regulated chemokine (TARC) plays an important role in the pathogenesis of atopic dermatitis (AD). We recently detected the single nucleotide polymorphism (SNP) (-431C>T) in the 5'-flanking region of TARC gene. OBJECTIVES: To examine whether the -431C>T SNP of the TARC gene is associated with susceptibility to AD and whether it affects the promoter activity of the TARC gene. METHODS: We investigated the genotype and allele frequencies of the SNP in 193 AD patients and 158 healthy controls by polymerase chain reaction-restriction fragment length polymorphism method. We compared the promoter activities between TARC promoter carrying 431C and that carrying -431T by transient-transfection assay in DJM-1 cell line. RESULTS: There were no significant differences in genotype or allele frequencies between AD patients and controls (genotype: P = 0.38, allele: P = 0.22). Luciferase activity was higher in -431T constructs than in -431C constructs (2.3-fold, P = 9.5 x 10(-6)). CONCLUSION: These results suggest that the -431C>T SNP of the TARC gene enhances the promoter activity of TARC gene but is not associated with susceptibility to AD in Japanese population.     

IL-33和IL1RL1基因单核苷酸多态性与特应性皮炎相关性研究

目的：分析IL-33和IL1RL1基因单核苷酸多态性(SNPs)与特应性皮炎（AD）的相关性。方法：PCR-SSP方法检测89例AD患者和138名正常对照组受试者IL-33和IL1RL1编码基因的等位基因和基因型频率。结果：AD患者的IL-33 rs1800925 C等位基因的频率高于对照组，而T等位基因和rs764706552等位基因G低于对照组（均P＜0.001）。IL-33 rs1800925基因型CC和rs764706552基因型CG与AD显著正相关（均P＜0.001）。两组患者的IL1RL1基因的等位基因和基因型频率无明显差异（均P＞0.05）。结论：IL-33基因可能与AD的发病相关。     

Analysis of GM-CSF gene polymorphisms (3606T/C and 3928C/T) in Japanese patients with atopic dermatitis

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is thought to play an important role in the pathogenesis of atopic dermatitis. To examine whether GM-CSF single nucleotide polymorphisms (SNPs) are associated with susceptibility to atopic dermatitis, we investigated the genotype and allele frequencies of the SNPs 3606T/C and 3928C/T of the GM-CSF gene in 181 Japanese patients with atopic dermatitis and 100 controls, using a PCR restriction fragment length polymorphism method. A strong linkage disequilibrium existed between the polymorphisms 3606 and 3928, suggesting two common GM-CSF haplotypes, 3606*T-3928*C and 3606*C-3928*T. However, there was no significant difference in genotype or allele frequencies between patients with atopic dermatitis and controls for either of the two polymorphisms, thus GM-CSF SNPs do not appear to be associated with susceptibility to atopic dermatitis in Japanese patients. A large-scale study is necessary to confirm these findings.     

Brain-derived neurotrophic factor gene polymorphisms and serum levels in Chinese atopic dermatitis patients

Background  Brain-derived neurotrophic factor (BDNF) plays an important role in the pathogenesis of atopic dermatitis (AD). Whether BDNF gene polymorphisms are associated with Chinese AD remains totally unknown.
Objective  The aim is to determine if BDNF gene C270T and G196A polymorphisms are associated with Chinese AD, and analyse the clinical relevance of BDNF gene polymorphisms and BDNF serum levels.
Methods  We conducted a case-control association analysis (160 patients and 169 controls) in Northern Chinese subjects. Genotyping was performed by restriction fragment length polymorphism, and serum levels of BDNF were measured using enzyme-linked immunosorbent assay.
Results  For C270T, there were significant differences in C/T genotype distribution ( P  = 0.003) and T allele frequencies ( P  = 0.004) between AD patients and controls in the whole dataset. Higher C/T genotype frequencies were found in male AD (10.6% vs. 1.1%, P  = 0.018) and in intrinsic AD (IAD; 15.79% vs. 2.91%, P  = 0.008). No association between G196A polymorphism and AD was observed in the whole cohort, while A allele was much more frequent in AD patients with atopy in first-degree relatives (65.8% vs. 34.2%, P  = 0.038). Serum BDNF levels were correlated with IAD severity as measured by Scoring Atopic Dermatitis index ( r  = 0.576, P  < 0.001).
Conclusion  T allele in C270T may be a risk factor for AD, especially in IAD and male AD. A allele in G196A may be a risk factor in AD patients with atopy in first-degree relatives. Serum BDNF levels were correlated with the severity of IAD.     

Polymorphisms within the C3 gene are associated with specific IgE levels to common allergens and super-antigens among atopic dermatitis patients

Abstract:  Atopic dermatitis (AD) is a chronic inflammatory skin disease. Twin and family studies suggest a strong genetic component of the disease. The keratinocytes secrete high amounts of C3 after stimulation with pro-inflammatory cytokines, which may play a functional role in skin inflammation. In this study, we genotyped four different single nucleotide polymorphisms (SNPs) by melting curve analysis using sequence specific hybridization probes in a well-characterized cohort of AD patients. Among four SNPs within C3 gene, higher frequencies of rs10410674 (23.5% vs 12.2%) and rs366510 (13.8% vs 6.5%) were observed in AD patients as compared with control group. None of the tested polymorphisms showed significant association with the risk of the disease phenotype. Analysis of rs10402876 SNP revealed its association with less severe AD disease expression (low SCORAD). Total serum IgE levels were not different among AD patients having any of the four SNPs. However, we observed significantly less serum-specific IgE levels to common allergens ( Dermatophagoides pteronyssinus and birch pollens) and Staphylococcal enterotoxin B in AD patients having rs366510 SNP. Thus, associations of polymorphism within C3 gene with less severe AD disease expression and a weaker sensitization to common allergens suggest the role of these SNPs in the development of AD.     

广西壮族、汉族系统性红斑狼疮与Toll样受体9基因多态性研究

目的 探讨TLR9单核苷酸多态性与广西系统性红斑狼疮（SLE）患者发病的相关性,以及其在壮族、汉两个民族间的差异。 方法 聚合酶链反应-限制性酶切技术、聚合酶链反应-限制性片段长度多态性分析技术（PCR-RFLP）对97例广西SLE患者和202例广西健康对照者的TLR9基因多态性进行检测,分析其基因型和等位基因频率与SLE部分临床实验室指标的关联性,并比较两民族间的差异。 结果 TLR9 rs352140CC、CT、TT基因型频率在汉族SLE组与汉族对照组中分别为42.9%、41.1%、16.1%和38.3%、55.8%、5.8%,差异有统计学意义（P < 0.05）,其C、T等位基因频率差异无统计学意义（P > 0.05）。TLR9rs352140 C/T基因型频率和等位基因频率在壮族SLE组与壮族健康对照组间、壮族SLE组与汉族SLE组间差异无统计学意义（均P > 0.05）。TLR9 rs352140TT基因型频率在ds-DNA阳性组比阴性组高（P < 0.05）,而T等位基因频率在两组间差异无统计学意义（P > 0.05）。TLR9 rs352140TT基因型频率和T等位基因的频率在SLEDAI ≥ 9组比SLEDAI < 9组高,差异有统计学意义（均P < 0.05）。TLR9 rs352140TT基因型频率和T等位基因的频率在ANA阳性组与阴性组间差异无统计学意义（均P > 0.05）。 结论 TLR9 rs352140基因多态性可能与广西汉族人SLE的易感性有关, TLR9基因多态性与部分SLE指标可能具有相关性。     

Correlation of serum total IgE, eosinophil granule cationic proteins, sensitized allergens and family aggregation in atopic dermatitis patients with or without rhinitis

Atopic dermatitis (AD) is a complex disease with both a genetic background and environmental interactions. Although multiple linkage-analyses about AD have been studied, there have been only a few family aggregation tests of AD or perennial allergic rhinitis (AR) to date. The association of allergen-specific IgE in AD and atopic dermatitis with allergic perennial rhinitis (ADR) have also been seldom discussed. The purpose of this study was to evaluate family aggregation and assess allergen-specific IgE in patients with AD and ADR. We also planned to investigate the effect of family history of AD on the prevalence of allergen-specific antibodies. The serum levels of IgE, eosinophil cationic protein (ECP) and major basic protein (MBP) were measured and compared in patients with AD and those with ADR. Proportional analysis compared allergen-specific IgE between AD and ADR. The family aggregation was conducted to estimate the odds ratio for various atopic diseases in different family members. Total IgE and allergen-specific antibodies in serum were compared between those patients who had AD with AR and those without. The result revealed that allergic rhinitis is the most common concomitant atopic disease associated with AD. The ADR group was more likely to have serum mite-, cockroach-, and feather-specific IgE. The positive rates for wheat, peanut and soybean were higher in those AD without rhinitis. In the family aggregation of AD, the odds ratio for siblings was higher than for parents, the ratios for brother and sister were 9.91 and 8.75, respectively. However, the odds ratio for parents of ADR was higher than siblings; the ratios for father and mother of ADR were 8.22 and 2.94, respectively. AD patients with family histories of AD were more likely to have mite-, soybean-, and peanut-specific antibodies in their serum. We concluded that aeroallergens are the most important allergens aggravating atopic diseases in Taiwan. Food plays an important role in the pathogenesis of AD. Measurement of serum total IgE combined with the MAST-CLA test could be helpful in the diagnosis of atopic diseases. The differential aggregation tendency for AD and ADR implicated the complexity of the gene-environment interaction in these atopic diseases.     

Association of DOCK8, IL17RA,and KLK12 Polymorphisms with Atopic Dermatitis in Koreans

BackgroundEarly-onset and severe atopic dermatitis (AD) in patients increase the probability of the development of allergic rhinitis or asthma. Treatment and prevention strategies in infants and young children with AD are targeted toward treating the symptoms, restoring skin barrier functions, and reducing the absorption of environmental allergens in an attempt to attenuate or block the onset of asthma and food allergy.ObjectiveGiven that the initiating events in AD remain poorly understood, identifying those at risk and implementing strategies to prevent AD is necessary.MethodsWhole-exome sequencing (WES) was performed in a 43 control group and a disease group with 20 AD patients without atopic march (AM) and 20 with AM. Sanger sequencing was carried out to validate found variants in cohorts.ResultsDOCK8, IL17RA, and KLK12 single-nucleotide polymorphisms were identified by WES as missense mutations: c.1289C>A, p.P97T (rs529208); c.1685C>A, p.P562G (rs12484684); and c.457+27>C, rs3745540, respectively. A case-control study show that total immunoglobulin E (IgE) level was significantly increased in the AA genotype of DOCK8 compared to the CA genotype in allergic patients. The rs12484684 of IL17RA increased risk of adult-onset AD (odds ratio: 1.63) compared to the control for (A) allele frequency. AD and AM Patients with the IL17RA CA genotype also had elevated IgE levels. rs3745540 of KLK12 was associated with AD in dominant model (odds ratio: 2.86).ConclusionDOCK8 (rs529208), IL17RA (rs12484684), and KLK12 (rs3745540), were identified using a new WES filtering method. the result suggests that polymorphism of DOCK8 and IL17RA might be related to increase the total IgE level.     

Interleukin-12 p40 gene (IL12B) 3'-untranslated region polymorphism is associated with susceptibility to atopic dermatitis and psoriasis vulgaris

Interleukin-12 (IL-12) is believed to play an important role in inducing Th1-type cytokine profiles. Atopic dermatitis (AD) and psoriasis vulgaris (PsV) are considered to be Th2 and Th1 type disease, respectively. The IL-12 p40 subunit gene (IL12B) is located at chromosome 5q31-33 and linkage findings of AD on 5q31 were reported. Recently single nucleotide polymorphism (SNP) (1188A/C) of IL12B has been reported. In function, it has been reported that this SNP is associated with IL12B mRNA expression levels. To learn whether this SNP is associated with susceptibility to AD or PsV, we investigated the genotype and allele frequencies of the SNP in AD patients, in PsV patients and in controls, examining 164 AD patients, 143 PsV patients and 100 healthy individuals in Japanese population. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. The A allele was decreased in AD patients (40.9%, p = 0.031) and increased in PsV patients (60.1%, p = 0.035) compared with controls (50.5%). This suggests that IL12B SNP is associated with susceptibility to AD and PsV, presumably by affecting the Th1/Th2 balance.     

儿童特应性皮炎IL-18基因启动子多态性与相关性研究

目的 检测儿童特应性皮炎患者外周血DNA中IL-18基因第2外显子上游启动子1第137和第607位点多态性，探讨其与儿童特应性皮炎发病的相关性。方法 从82例重庆汉族儿童特应性皮炎患者及健康对照组100例的抗凝血中提取DNA，用序列特异性引物PCR扩增技术（PCR-SSP）及PCR产物直接测序法鉴定基因类型，对结果进行统计学分析处理。结果 IL-18基因第2外显子的第137位点核苷酸存在G、C二态性，可表现为GG纯合、CC纯合、GC杂合三种基因型；第607位点核苷酸存在C、A二态性，可表现为CC纯合、AA纯合、CA杂合三种基因型。IL-18-137G/C基因型分布在患者组和对照组间差异有统计学意义，患者组137C等位基因频率显著高于对照组（χ2 = 4.54，P = 0.033），137C等位基因在重度组中分布频率显著高于轻度组（χ2 = 3.93，P < 0.05）；IL-18-607位点等位基因频率在轻度、中度、重度组及对照组之间分布差异无统计学意义（P > 0.05）；IL-18-137G/C位点C等位基因在病例与对照组比较，优势比OR = 1.76，137G/C基因型的优势比OR = 2.33。结论 儿童IL-18基因第2外显子上游启动子1第137和第607位点存在单核苷酸多态性，IL-18-137G/C是特应性皮炎患儿的候选易感基因。     

特应性皮炎与HLA-DRB1 DQB1基因的相关性研究

目的探讨HLA-DRB1和DQB1位点基因与汉族特应性皮炎的相关性。方法用序列特异性引物-聚合酶链反应(PCR-SSP)方法,对59例特应性皮炎患者(来自27个家系)和60例正常对照者进行了HLA-DRB1和DQB1等位基因的分型,并分析了DRB1和DQB1基因在各组中的分布。结果特应性皮炎患者组DRB1*15,DR7,DQB1*0601等位基因频率较正常对照组增高(P<0.05);特应性皮炎患者组DQB1*0302频率较正常对照组降低(P<0.05)。特应性皮炎家系成员中对屋尘螨抗原皮试阳性者HLA-DR7等位基因频率较皮试阴性者均显著增高(P<0.05)。结论特应性皮炎的发病可能与DRB1*15,DR7,DQB1*0601相关;DQB1*0302对特应性皮炎的发病可能起保护作用。HLA-DR7在限定对屋尘螨抗原特异性IgE反应过程中起重要作用。     

CARD15/NOD2 single nucleotide polymorphisms do not confer susceptibility to type I psoriasis

BACKGROUND: A psoriasis susceptibility locus on chromosome 16q was identified recently. This region coincides with a locus predisposing to Crohn's disease. Patients with Crohn's disease have a fivefold greater relative risk for development of psoriasis. In Crohn's disease mutation of the caspase recruitment domain family, member 15 (CARD15) gene (chromosome 16q12.1) confers susceptibility. In light of the overlap in linkage data, and the observation of comorbidity between Crohn's disease and psoriasis, it is plausible that both diseases share a common genetic factor. OBJECTIVES: To assess the genetic contribution of CARD15 single nucleotide polymorphisms (SNPs) in the pathogenesis of type I psoriasis. METHODS: Eight SNPs in CARD15 were genotyped in 148 patients with type I psoriasis and 192 unrelated controls, following a test for population stratification. Genotype and allele frequencies were compared along with estimated SNP haplotype frequencies. RESULTS: No differences were observed in genotype allele or haplotype frequencies between the case and control cohorts. CONCLUSIONS: The most complete assessment of CARD15 SNPs in type I psoriasis to date reveals no evidence of association to type I psoriasis.     

An association between IL-9 and IL-9 receptor gene polymorphisms and atopic dermatitis in a Korean population

Background

The genes encoding IL-9 and IL-9R have recently been implicated in the genetic basis of asthma and allergy. Although studies performed on transgenic and knockout mice have shown conflicting results, no evidence of skin changes has ever been reported in these animals.

Objective

To find association of the SNPs in IL-9 and IL-9R genes and interaction of these genes in atopic dermatitis.

Method

We genotyped 5 SNPs from the IL-9 and IL-9R genes of 1090 subject samples (631 AD patients and 459 normal controls). A luciferase assay was then performed for the rs31563 (−4091G/A) SNP located in the IL-9 gene promoter region.

Result

The rs31563 (−4091G/A) SNP in the IL-9 gene was significantly associated with the AD phenotype, especially allergic-type AD. In the luciferase assay, the rs31563 G construct was observed to have 1.54 times higher activity than the rs31563 A construct. Although no association was found between SNPs in IL-9R gene and AD, the rs3093467 SNP showed association with non-allergic AD. In the gene-gene interaction analysis, we found that IL-9/IL-9R genotype rs31563 GG/rs3093467 TT conveyed a greater risk for AD phenotype development.

Conclusion

Significant evidence exists to suggest that the rs31563 SNP (−4091G/A) located in the IL-9 gene is associated with an increased susceptibility to AD. Similarly, the rs3093467 SNP in IL-9R gene seems to be associated with an increased risk for developing non-allergic AD. In a subsequent gene-gene interaction analysis, the rs31563 GG/rs3093467 TT genotype combination (IL-9/IL-9R) was found to exert a synergistic effect in the development of the AD phenotype. As the classes of helper T cells are diverse and the function of IL-9 cytokine has not been fully described, the cutaneous function of IL-9 needs to be further explored in future studies.     

Heterogeneity of serum IgE levels in atopic dermatitis

To determine whether serum IgE levels in patients with atopic dermatitis (AD) have a relationship to familial background of atopic respiratory disease (ARD), serum IgE levels were measured in 50 AD patients who had personal history of ARD, 37 AD patients who did not have personal history of ARD but had family history of ARD, and 52 "pure" AD patients who had neither personal nor family history of ARD. The "pure" AD patients showed significantly lower serum IgE levels than AD patients who had personal or family history of ARD. It is suggested that AD patients may be classified into at least two subgroups: those with ARD predisposition who have an enhanced IgE producing potential, and those without ARD predisposition who have a low or not-enhanced ability for IgE production.     

Beta defensin‐1 gene (DEFB1) polymorphisms are not associated with atopic dermatitis in children and adolescents from northeast Brazil (Recife,Pernambuco)

Background Atopic dermatitis (AD) is a common inflammatory skin disease resulting from the interplay between environmental, immunological and genetic factors. In our study, we investigated the role of three single nucleotide polymorphisms (SNPs) at 5′‐UTR of DEFB1 gene, encoding for the human beta defensin‐1, on the susceptibility to develop AD in a group of Brazilian children and adolescents. Methods Three SNPs, ?20 G/A (rs11362), ?44 C/G (rs1800972), and ?52 G/A (rs1799946) at 5′‐UTR of DEFB1 gene were genotyped in two groups of children and adolescents, one affected by AD (96 subjects), the other healthy (191 individuals), from northeast Brazil. Results ?44 C/G frequencies were comparable between the two groups. The ?20 GG genotype was more frequent in AD subjects than in healthy controls; the ?52 GG, conversely, was more frequent in healthy controls than in AD. However, both these differences did not reach statistical significance. Also, association between SNPs and AD severity has been shown. The analysis of DEFB1 haplotypes did not highlight any association of the three SNPs with AD development or disease severity. Conclusions Our results seem to exclude a role for the ?44 C/G DEFB1 SNPs on the pathogenesis and severity of AD, while for the ?20 C/G and ?52 G/A, even if not statistically significant, we evidenced a slight trend for susceptibility (?20 GG) and protection (?52 GG) for the development of AD. However, as controversial findings have been reported in the literature, the role of DEFB1 in the development of AD and in the severity of the phenotype deserves further investigation.