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.     

Netherton syndrome in two Japanese siblings with a novel mutation in the SPINK5 gene: immunohistochemical studies of LEKTI and other epidermal molecules

BACKGROUND: Netherton syndrome (NS) is a severe autosomal recessive disorder characterized by ichthyosiform erythroderma, bamboo hair and atopy. The disease is caused by mutations in the SPINK5 gene, which encodes a putative serine protease inhibitor, LEKTI (lymphoepithelial Kazal-type-related inhibitor). Previous studies have clearly shown a crucial role for LEKTI in skin barrier formation. OBJECTIVES: To identify pathogenic mutations in two Japanese siblings with NS, and further to investigate the consequences of the mutations at the protein level. METHODS: To screen for mutations in the SPINK5 gene, all of its exons and splice junctions were amplified by polymerase chain reaction and directly sequenced. In addition, immunohistochemical staining of LEKTI, desmoglein (Dsg) 1 and elafin was performed with their specific antibodies. RESULTS: Mutation analysis resulted in the identification of compound heterozygous mutations, Q713X and R790X, in the SPINK5 gene of both patients. The former one is a novel mutation. Immunohistochemical studies in one patient demonstrated a complete absence of LEKTI and a strong expression of elafin in the patient's skin. Dsg1 was normally expressed in our patient. CONCLUSIONS: In this report, we describe compound heterozygous mutations in the SPINK5 gene in two Japanese siblings with NS. The result of immunohistochemistry shows LEKTI deficiency and upregulation of elafin in the skin of one patient. Furthermore, our data indicate that degradation of Dsg1 does not always occur in NS.     

Netherton syndrome in one Chinese adult with a novel mutation in the SPINK5 gene and immunohistochemical studies of LEKTI

Background:

Netherton syndrome (NS) is a severe autosomal recessive ichthyosis. It is characterized by congenital ichthyosiform erythroderma, trichorrhexis invaginata, ichthyosis linearis circumflexa, atopic diathesis, and frequent bacterial infections. The disease is caused by mutations in the SPINK5 (serine protease inhibitor Kazal-type 5) gene, a new type of serine protease inhibitor involved in the regulation of skin barrier formation and immunity. We report one Chinese adult with NS. The patient had typical manifestation of NS except for trichorrhexis invaginata with an atopic diathesis and recurrent staphylococcal infections since birth.

Aims:

To evaluate the gene mutation and of its product activity of SPINK5 gene in confirmation of the diagnosis of one Chinese adult with NS.

Materials and Methods:

To screen mutations in the SPINK5 gene, 33 exons and flanking intron boundaries of SPINK5 were amplified with polymerase chain reaction (PCR) and used for direct sequencing. In addition, immunohistochemical staining of LEKTI (lymphoepithelial Kazal-type-related inhibitor) with specific antibody was used to confirm the diagnosis of NS. The results were compared with that of healthy individuals (twenty-five blood samples).

Results:

A G318A mutation was found at exon 5 of patient''s SPINK5 gene which is a novel missense mutation. The PCR amplification products with mutation-specific primer were obtained only from the DNA of the patients and their mother, but not from their father and 25 healthy individuals. Immunohistochemical studies indicated there was no LEKTI expression in NS patient''s skin and there was a strong LEKTI expression in the normal human skin.

Conclusion:

In this report, we describe heterozygous mutation in the SPINK5 gene and expression of LEKTI in one Chinese with NS. The results indicate that defective expression of LEKTI in the epidermis and mutations of SPINK5 gene are reliable for diagnostic feature of NS with atypical clinical symptoms.     

A heterozygous null mutation combined with the G1258A polymorphism of SPINK5 causes impaired LEKTI function and abnormal expression of skin barrier proteins

Background  Loss-of-function mutations in the Kazal-type serine protease inhibitor, LEKTI, encoded by the SPINK5 gene cause the rare autosomal recessive skin disease Netherton syndrome (NS). G1258A polymorphism in SPINK5 may be associated with atopic dermatitis, which shares several clinical features with NS.
Objectives  To determine if the phenotype of NS can be caused by a single null mutation in SPINK5 combined with the homozygous G1258A polymorphism.
Methods  We screened mutations in the gene SPINK5 by direct DNA sequencing and position cloning and examined the expressions of the SPINK5 -encoded protein LEKTI and other relevant proteins by immunostaining and immunoblot.
Results  We describe here a patient who was clinically diagnosed with NS and carried a single null mutation in SPINK5 combined with the homozygous G1258A polymorphism. SPINK5 mRNA was present at normal levels and LEKTI was expressed in the epidermis. Nonetheless, the putative downstream LEKTI substrates stratum corneum trypsin-like enzyme (SCTE), desmoglein 1 and protein markers of keratinocyte differentiation were expressed abnormally, similar to that seen in NS if two null mutant alleles are present.
Conclusion  This finding indicates that haploinsufficiency of SPINK5 can cause the NS phenotype in the presence of one null mutation with homozygous G1258A polymorphisms in SPINK5 , and this could impair the function of LEKTI and therefore acts as a true mutation.     

Hint for association of single nucleotide polymorphisms and haplotype in SPINK5 gene with atopic dermatitis in Koreans

Clinical studies, including twin studies, support the concept that the risk of atopic dermatitis (AD) may be mediated through skin-specific genes, rather than simply through systemic immune or atopy risk genes. The SPINK5 gene is expressed on epithelial surfaces and may provide protection against other allergenic serine proteases. Mutations in the SPINK5 gene result in Netherton syndrome, a disorder characterised by AD, ichthyosis, and elevated serum IgE levels. We genotyped 21 single nucleotide polymorphisms (SNPs) from the SPINK5 gene for 1090 case-control samples (631 patients with AD and 459 normal controls) and analysed the SNPs and haplotypes in this gene and also searched for gene-gene interactions between SPINK5 and the DEFB1 gene that we previously reported. Six SNPs [rs17718511 (P = 0.026), rs17860502 (P = 0.024), KN0001820 (P = 0.045), rs60978485 (P = 0.007), rs17718737 (P = 0.02), and rs1422985 (P = 0.038)] and the haplotype TAA (rs60978485, rs6892205, rs2303064; P = 0.023) in the SPINK5 gene showed significant different allelic or genotypic distributions between the AD group and the control group. We also found that four SNPs [rs17718511 (P = 0.033), rs17860502 (P = 0.031), rs60978485 (P = 0.005), rs17718737 (P = 0.023)] and the haplotype TAA (P = 0.02) in the SPINK5 gene showed associations with the susceptibility of the allergic type of AD (ADe). In addition to this finding, we speculate that the SNPs from DEFB1 and SPINK5 affect the individual susceptibility to development of ADe in an additive manner. This study provides evidence for a significant interaction between allergens and the SPINK5 gene that may contribute to ADe susceptibility.     

A Japanese infant with localized ichthyosis linearis circumflexa on the palms and soles harbouring a compound heterozygous mutation in the SPINK5 gene

We report a 6-month-old Japanese boy showing ichthyosis linearis circumflexa localized on the palms and soles. He showed bamboo hairs and aminoaciduria, and was positive for cow's milk and egg IgE antibodies by radioallergosorbent tests. Trypsin-like hydrolytic activity in the patient's lesional stratum corneum showed an activity seven times higher than that in age-matched controls. DNA analysis showed that the patient harboured the compound heterozygous mutations R790X and 1220+1 G-->C in the SPINK5 gene, compatible with the diagnosis of Netherton syndrome (NS). As the genotype/phenotype correlations in NS have not yet been fully clarified, the position of the premature termination codon in the SPINK5 gene may contribute to explain such a mild form of NS in our patient.     

Serine protease inhibitor lymphoepithelial Kazal type-related inhibitor tends to be decreased in atopic dermatitis

Background  A pathogenic role of serine protease inhibitor lymphoepithelial Kazal type-related inhibitor (LEKTI) in atopic dermatitis (AD) is currently in intense debate. Analyses of an association between genetic polymorphisms of SPINK5 and atopic diseases revealed contradictory results. Herein, we assessed the role of LEKTI in AD at an expressional and functional level.
Methods  The expression of LEKTI and its inhibitory capacity was measured by real-time polymerase chain reaction and hydrolytic activity assay, respectively, in keratinocyte cell cultures of three AD patients in comparison to cultures of healthy individuals (5×) and Netherton (NS) patients (3×).
Results  Expression of LEKTI was significantly decreased in AD vs. healthy volunteers. Due to reduced protease inhibition, trypsin-like hydrolytic activity in AD was slightly increased, although not significantly.
Conclusions  Even though the number of investigated subjects was small and hydrolytic activity was only slightly increased, the results denote that LEKTI might be diminished in AD. The study also disclosed the necessity of functional analyses in addition to genetic investigations to gain further and more detailed insights into the role of LEKTI in AD.     

Netherton syndrome: report of two Taiwanese siblings with staphylococcal scalded skin syndrome and mutation of SPINK5

Netherton syndrome (NS) is a severe autosomal recessive ichthyosis. It is characterized by congenital ichthyosiform erythroderma, trichorrhexis invaginata, ichthyosis linearis circumflexa, atopic diathesis and frequent bacterial infections. Pathogenic mutations in SPINK5 have recently been identified in NS. SPINK5 encodes lymphoepithelial Kazal-type-related inhibitor (LEKTI), a new type of serine protease inhibitor involved in the regulation of skin barrier formation and immunity. We report two Taiwanese brothers with NS. The patients had typical manifestations of NS with an atopic diathesis and recurrent staphylococcal infections, including staphylococcal scalded skin syndrome (SSSS) since birth. Horny layers were obtained by skin surface biopsy for electron microscopy from lesional skin of both patients and from normal controls. All 33 exons and flanking intron boundaries of SPINK5 were amplified for direct sequencing. The ultrastructure of the stratum corneum (SC) was characterized by premature degradation of corneodesmosomes (CDs) with separation of corneocytes. A homozygous 2260A --> T (K754X) mutation of SPINK5 was found in both patients. Staphylococcal exfoliative toxin A (ETA) is a serine protease capable of cleaving desmoglein 1, an important adhesive molecule of CDs, and can cause separation of the SC, resulting in SSSS. The premature degradation of CDs found in our patients may be attributable to insufficient LEKTI, and possibly also to colonization/infection of ETA-producing Staphylococcus aureus. Mechanisms involved in the pathogenesis of the skin barrier defect in NS are proposed. Further study is needed to prove this hypothesis.     

A family study of atopic dermatitis

Summary The history of 188 Caucasian patients with atopic dermatitis (AD) and of 2,151 family members has been analyzed. Of the AD patients 48% suffered from respiratory atopy (36% rhinitis, 28% asthma, and 15% both). AD showed by far the earliest onset of all atopic diseases: 50% of our patients had skin lesions before the age of 2 years and 60% before the age of 5 years. In contrast, symptoms of allergic asthma developed in 40% of AD patients before the age of 5 years in comparison with only 25% who had allergic rhinitis. AD affects females more frequently than males (male to female ratio 11.5), regardless of whether additional respiratory atopies are present or not. In contrast, respiratory atopies develop more frequently in males than in females (male to female ratio 1.51). Mothers with respiratory atopy more often have atopic children (26%) than do fathers with respiratory atopy (13%). Finally, risk figures for genetic counselling are given. In short, the general risk of developing AD (3%) and atopy (7%) increases by a factor of two with each first-degree family member already suffering from atopy.     

Analysis of SPINK 5, KLK 7 and FLG genotypes in a French atopic dermatitis cohort

The role of a genetically impaired epidermal barrier as a major predisposing factor in the pathogenesis of atopic disorders is currently under closer investigation. Variants on three candidate genes (SPINK5, KLK7 and FLG) have been associated with atopic dermatitis. A functional relevance has already been established for filaggrin variants, but not for SPINK5 and KLK7 polymorphisms. The objectives of this study were to confirm the association between SPINK5, KLK7, FLG variants and atopic dermatitis and to assess how variants influence selected phenotypic traits. This cross-sectional study was carried out over 20 months in 99 children and adults with atopic dermatitis (median age 7 years). The following items were analysed: SCORAD, TEWL, ichthyosis vulgaris, presence of asthma, total IgE serum levels. The SPINK5 E420K SNP, the KLK7 4bp insertion polymorphism and the filaggrin mutants (R510X and 2282del4) were analysed as described previously. The control group for genetic analysis was recruited in an ethnically matched, phenotypically anonymous cohort (n=102). The allelic frequencies were 0.525 for SPINK5, 0.26 for KLK7 polymorphisms, 0.101 and 0.075 for 2282del4 and R501X FLG mutants, respectively. The association of atopic dermatitis with filaggrin variants was confirmed, but not that of SPINK5 or KLK7 polymorphisms. SCORAD and TEWL measurements were not influenced by any of the variants. The SPINK5 polymorphism was associated with high IgE serum levels (p=0.011). Abnormal barrier genes do not influence the severity of atopic dermatitis. The SPINK5 gene polymorphism may modulate systemic immune effects favouring the IgE response to atopens. TEWL does not allow the characterization of subsets of patients with or without abnormal barrier genes.     

Netherton综合征一例SPINK5基因突变研究

目的 检测Netherton综合征患者SPINK5基因的突变情况。 方法 收集患者临床资料,提取患者及其相关亲属外周血DNA,用PCR扩增SPINK5基因编码区的全部外显子及其侧翼序列并测序。 结果 直接测序发现患者SPINK5基因的第13号外显子中的第1111位碱基发生C→T杂合突变（c.1111C > T）,导致其编码第371位氨基酸变为终止密码子（p.R371X）;第32号外显子中的第3121位碱基发生C→T杂合突变（c.3121C > T）,导致其编码第1041位氨基酸发生错义突变（p.R1041C）,其健康父母为相应突变的杂合携带者,200例健康对照未见该突变。 结论 SPINK5基因的p.R371X及p.R1041C复合杂合突变可能是引起该患者临床表现的病因之一。     

Netherton syndrome: mutation analysis of two Taiwanese families

Netherton syndrome (NS) is a severe autosomal recessive skin disorder characterized by congenital ichthyosiform erythroderma, hair shaft abnormalities, and atopic diathesis. Recently, pathogenic mutations were identified in serine protease inhibitor Kazal-type 5 (SPINK5), the gene that encodes lympho-epithelial Kazal-type related inhibitor (LEKTI), a type of serine protease inhibitor involved in the regulation of skin barrier formation and immunity. In the present report, we describe the mutation analysis of two Taiwanese patients with NS. Patient 1 has heterozygous mutations; the maternal allele has novel T808I (C–T transition in codon 808) and the paternal allele has recurrent R790X (C–T transition in codon 790). Patient 2 is homozygous for a novel polymorphism R267Q (G–A transition in codon 267). The change was not detected in the patient’s father. Haplotype analysis revealed that the patient was homozygous for the 5 single nucleotide polymorphisms in the genomic sequence of SPINK5 as well as the flanking (GT)₁₇ and D5S413, in addition to the discrepancy of R267Q. Nevertheless real-time quantitative PCR analysis revealed no microdeletion in the genomic sequence of SPINK5. Thus uniparental disomy of maternal SPINK5 allele was indicated. Shuan-Pei Lin and Shu-Yi Huang contributed equally to this work.     

New homozygous SPINK5 mutation, p.Gln333X, in a Turkish pedigree with Netherton syndrome

Netherton syndrome (NS) is a rare autosomal recessive genodermatosis caused by loss-of-function mutations in the SPINK5 gene. The clinical features include congenital ichthyosis, trichorrhexis invaginata and atopy. In this study, we report a new homozygous SPINK5 mutation, p.Gln333X, responsible for NS in affected members of two closely related Turkish families, and provide an overview of the genotype-phenotype correlation in this condition.     

Reduced allergy rates in atopic eczema to contact allergens used in both skin products and foods: atopy and the 'hapten-atopy hypothesis'

Background:  Food allergy is strongly associated with atopy. This retrospective study investigates whether atopic status affects responses to contact allergens also found in food. We compared incidences of atopic dermatitis/eczema (AD) in subjects who were patch-test positive (PT+) to diallyl disulfide from handling garlic and parabens used as a skin cream/ointment and food preservative with the incidence in those subjects who were PT+ to chemicals encountered at skin surfaces (lanolin and nickel).
Results:  36 658 patients with eczema/dermatitis were patch tested (1980–2006). 10 326 (28.2%) had AD. 13/83 (15.6%) PT+ subjects to diallyl disulfide/garlic had AD (AD/total population versus AD/diallyl disulfide PT+, P  = 0.011). 54/239 parabens PT+ had AD (22.6%), while 181/608 lanolin PT+ had AD (29.8%) ( P  < 0.05).
Conclusions:  Contact allergy to haptens with oral and skin exposure is reduced in AD compared with non-AD, unlike food protein hypersensitivity. Lanolin frequency was not decreased. Possible explanations include (i) confounding factors, e.g. AD subjects handle garlic less than non-AD subjects, or (ii) AD patients tolerate haptens efficiently, secondary to their atopic status, or (iii) oral tolerance of haptens antagonizes tolerance of food proteins, contributing to development of atopy (hapten-atopy hypothesis). The recent upsurge of atopy took place when gut exposure to haptens in processed foods increased dramatically.     

Interleukin 4 receptor alpha chain polymorphism Gln551Arg is associated with adult atopic dermatitis in Japan

Localization of a locus for atopy to chromosome 16p12-p11 and reported associations of Ile50Val and Gln551Arg polymorphisms in interleukin-4 receptor alpha chain (IL 4R gene) with atopy prompted us to sequence the gene in 27 adult atopic dermatitis (AD) and 29 non-atopic (non-AD) subjects. Among six known polymorphisms, Gln551Arg was significantly associated with AD (P = 0.01). This polymorphism was found to be heterozygous in six of 27 patients with AD but none of the 28 non-AD controls. Ile50Val, which was previously reported to be associated with atopic asthma in Japan, showed no association with AD in our group. Glu375Ala and Cys406Arg also showed no association with AD. The IL 4R gene should thus be considered a compelling candidate gene for AD.     

Association between non‐atopic hand eczema and interleukin‐13 gene polymorphism in Taiwanese nursing population

Chronic hand eczema is an important occupational skin disease with atopic dermatitis (AD) and wet work being the most important risk factors. This study was launched to analyse the potential association between AD‐related inflammation genes and development of non‐atopic hand eczema among nurses in University Hospital. Atopic eczema, non‐atopic hand dermatitis and control groups were identified. The association between occurrence of non‐atopic hand eczema and interleukin (IL)‐13, IL‐4 and IL‐5 gene variants was analysed. IL13 rs20541 A allele [assuming recessive model; odds ratio (OR) = 3.38, 95% CI: (1.63–7.00)] showed association with development of non‐atopic hand eczema. Additive score analyses showed combination of this gene variant with previously identified risk factors including certain SPINK5 polymorphism and more than 10 years of work experience conferred highest risk for development of non‐atopic hand eczema. As non‐atopic hand eczema made up significant portion of occupational skin diseases, further studies should be focused on this commonly encountered skin condition.     

Distinct SPINK5 and IL-31 polymorphisms are associated with atopic eczema and non-atopic hand dermatitis in Taiwanese nursing population

Abstract: The term ‘hand dermatitis’ describes inflammatory skin condition localized to the hands. Nurses working at hospital settings are prone to develop hand dermatitis. The current study aimed to evaluate whether certain genetic polymorphisms were associated with the development of atopic eczema or non‐atopic hand dermatitis in Taiwanese population. Nurses of Kaohsiung Medical University Hospital were recruited. Atopic eczema, non‐atopic hand dermatitis and normal control groups were identified. The serine protease inhibitor Kazal type 5 (SPINK5), filaggrin and interleukin‐31 (IL‐31) gene variants were compared between the diseased and control groups. Our results showed that rs2303070 T allele of SPINK5 (assuming recessive model; OR = 3.58, 95% CI 1.63–7.84; P = 0.0014) and rs7977932 G allele of IL‐31 (assuming recessive model; OR = 18.25, 95% CI = 3.27–101.94; P = 0.0009) were associated with increased risks of developing atopic eczema, while rs6892205 G allele of SPINK5 (assuming dominant model; OR = 3.79, 95% CI 1.55–9.28; P = 0.0036) was associated with the development of non‐atopic hand dermatitis. In summary, our results showed that distinct SPINK5 and IL‐31 gene variants were associated with the development of atopic eczema and non‐atopic hand dermatitis. The barrier function, particularly those regulated by SPINK5, may play an important role in the development of both atopic eczema and non‐atopic hand dermatitis.     

Association of atopic dermatitis to the beta subunit of the high affinity immunoglobulin E receptor

IgE dysregulation is a major pathogenic feature of atopic dermatitis and other IgE-mediated allergic diseases such as asthma and rhinitis. Allergen complexed to IgE binds to the high affinity receptor for IgE (FcεRI) on the surface of epidermal Langerhans cells, mast cells and basophils, triggering the release of inflammatory mediators. The β subunit of FcεRI has been localized to human chromosome 11q12–13, and variants within this gene have been shown to associate with asthma and measures of atopy. We have tested several polymorphisms within FcεRI-β for association to atopic dermatitis in a panel of 60 families (panel A), recruited through a proband with atopic dermatitis. The findings were tested in a second panel of families (panel B). Significant sharing of maternal alleles was seen for atopic dermatitis and allele 2 of Rsa I intron 2 ( Rsa I _in2*2 ) ( P  = 0.0022) and allele 1 of Rsa I exon 7 ( Rsa I _ex7*1 ) ( P  = 0.0036) FcεRI-β gene polymorphisms. These findings were replicated in Panel B, confirming the association of FcεRI-β Rsa I polymorphisms with atopic dermatitis. The combined significance of the association of atopic dermatitis to Rsa I polymorphisms was P  = 0.0002 ( Rsa I _in2*2 ) and P  = 0.00034 ( Rsa I _ex7*1 ). The polymorphisms also showed association with asthma: P  = 0.0068 ( Rsa I _in2*2 ) and P  = 0.018 ( Rsa I _ex7*1) . Polymorphisms within the FcεRI-β gene are strongly associated with atopic dermatitis.