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1.
Tsunemi Y Saeki H Nakamura K Sekiya T Hirai K Fujita H Asano N Tanida Y Kakinuma T Wakugawa M Torii H Tamaki K 《Journal of dermatological science》2002,29(3):222-228
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. 相似文献
2.
Association of SPINK5 gene polymorphisms with atopic dermatitis in the Japanese population 总被引:10,自引:0,他引:10
Kato A Fukai K Oiso N Hosomi N Murakami T Ishii M 《The British journal of dermatology》2003,148(4):665-669
BACKGROUND: Netherton's syndrome (NS) is an autosomal recessive disorder characterized by trichorrhexis invaginata ('bamboo hair'), congenital ichthyosiform erythroderma and an atopic diathesis. NS has recently been shown to be due to a defect in the SPINK5 gene, encoding LEKTI, a 15-domain serine protease inhibitor. SPINK5 maps to chromosome 5q31-q32, and has been suggested to be a locus predisposing to atopy in general. Recently, coding polymorphisms in SPINK5 exons 13 and 14 have been reported to be associated with atopy, asthma and atopic dermatitis (AD). OBJECTIVES: To examine whether these polymorphisms are also associated with AD in Japan. METHODS: We characterized eight polymorphisms in SPINK5 exons 13 and 14 in 124 Japanese patients with AD and 110 healthy controls. The polymorphisms we examined were IVS12-26C-->T, IVS12-10A-->G, 1103A-->G (Asn368Ser, in exon 13), 1156G-->A (Asp386Asn, in exon 13), 1188T-->C (His396His, in exon 13), IVS13-50G-->A, 1258G-->A (Glu420Lys, in exon 14) and IVS14+19G-->A. RESULTS: We found significant associations between seven of these polymorphisms and AD in Japanese patients. CONCLUSIONS: This study confirms the previous suggestion of an association between SPINK5 and AD. 相似文献
3.
E. M. J. Peters A. Kuhlmey M. Knackstedt R. Paus B. F. Klapp P. C. Arck 《Experimental dermatology》2004,13(9):590-590
IgE levels are not elevated in about 20% of patients with atopic dermatitis (AD). In this intrinsic AD (IAD), allergic mechanisms are not very important and pathogeny could be mainly neurogenic. β2-adrenergic receptors are localized on cells involved in AD: Langerhans' cells, keratinocytes and lymphocytes. We wondered whether IAD could be associated with gene polymorphisms 16 and 27 of this receptor. We studied 98 healthy subjects and 83 subjects suffering from DA (UKWP criteria). IgE levels were normal in 12 of them and elevated in 71 (EAD). After DNA extraction, the genotyping was done by PCR and Direct Sequencing of candidate gene. Statistical analysis was performed with EPI-INFO 6.04 for χ2 test. We found a significant association of Gln27Glu polymorphism with IAD ( P = 0.00071 and χ2 = 14.51). There was no difference between healthy subjects and EAD patients. Adrenergic receptor agonists are known to attenuate the proliferative response of human lymphocytes after activation, through the inhibition of interleukin-2 release. It is known that catecholamines inhibit the antigen-presenting capability of epidermal Langerhans' cells. Long-term agonist-promoted downregulation of receptor number is absent when glu is at position 27. We suggest that the suppression of inhibiting effects of catecholamines could be involved in IAD pathogeny. Dichotomic nature of AD (EAD and IAD) is also associated with polymorphisms (SNP) of the interleukin-4/interleukin-13 receptor gene and the differences of cutaneous variables (transepidermal water loss, capacitance and pH). Altogether, these findings indicate that IAD patients exhibit phenotypic and also genotypic features which differ from those patients with EAD. Otherwise, the presence of this polymorphism could provide an explication of rarity of hypertension with AD, because Glu27Gln has been identified as a susceptibility polymorphism for HTA. 相似文献
4.
Tsunemi Y Komine M Sekiya T Saeki H Nakamura K Hirai K Kakinuma T Kagami S Fujita H Asano N Tanida Y Wakugawa M Torii H Tamaki K 《Experimental dermatology》2004,13(11):715-719
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. 相似文献
5.
Phenotyping of epidermal dendritic cells allows the differentiation between extrinsic and intrinsic forms of atopic dermatitis 总被引:6,自引:0,他引:6
Oppel T Schuller E Günther S Moderer M Haberstok J Bieber T Wollenberg A 《The British journal of dermatology》2000,143(6):1193-1198
Atopic dermatitis (AD) is a clinically characteristic, chronic inflammatory skin disease of unknown origin. IgE-mediated uptake and antigen focusing of environmental allergens by dendritic cells (DCs) is assumed to be a central immunopathogenetic event. A so-called intrinsic type of AD (IAD) has been delineated from the more common extrinsic AD (EAD) by normal serum IgE levels, negative RAST tests and negative immediate-type skin reactions towards environmental allergens. The recently characterized human autoantigen Hom S 1 has been proposed to play a part in the pathogenesis of IAD. OBJECTIVES: To compare clinical and laboratory data between patients with IAD and EAD, and to investigate potential differences in the inflammatory micromilieu of the epidermal compartment in IAD and EAD lesions. METHODS: Epidermal DC phenotyping, a recently validated technique based on the three-colour flow cytometric analysis of Langerhans cells and the so-called inflammatory dendritic epidermal cells from epidermal single-cell suspensions, was performed on samples from 69 patients with AD (seven with IAD and 62 with EAD) and 94 controls. RESULTS: Patients with EAD tended to have an earlier onset of disease but similar disease duration and family history of atopic diseases. Quantitative analysis of CD36 expression on DCs as a marker of inflammation, as well as the percentage of inflammatory dendritic epidermal cells in the CD1a+ epidermal DC pool, indicated a comparable disease activity in IAD and EAD. EAD was characterized by a significantly higher FcepsilonRI expression on the CD1a+ epidermal DCs than IAD. Using the FcepsilonRI/FcgammaRII expression ratio as a disease marker for AD, values for IAD fell below the diagnostic cut-off level of 1.5 for this ratio. CONCLUSIONS: While IAD is clinically similar to EAD, the inflammatory microenvironment in this condition seems different from classical EAD and can be distinguished by phenotyping of epidermal DCs. 相似文献
6.
Background: Although most patients with atopic dermatitis (AD) show high total and allergen-specific serum immunoglobulin E (IgE) levels, a small subgroup of AD patients have normal total IgE levels and negative serum allergen-specific IgE. This subgroup has been termed 'intrinsic' AD (IAD) as a counterpart to 'extrinsic' AD (EAD). However, the difference of chemokines between IAD and EAD has not yet been evaluated.
Objective: We investigated the expression of CC chemokine ligand (CCL) 17, CCL22, and CCL18 in patients with IAD and EAD, which are known to be highly expressed in AD patients.
Methods: We assessed the protein levels of these chemokines in peripheral blood mononuclear cells (PBMCs), sera and lesional skins. We also evaluated CCL18 mRNA levels in monocytes, Langerhans cell (LC)-like dendritic cells (DCs) and inflammatory dendritic epidermal cell (IDEC)-like DCs from both types of AD patients.
Results: There were no significant differences in CCL17 and CCL22 expression in PBMCs, sera and lesional skins of patients with IAD and EAD. CCL18 expression did not differ in PBMCs, sera and LC-like DCs from the two subgroups, but strong CCL18 expression was observed in lesional skins and IDEC-like DCs in patients with EAD. Lastly, serum CCL18 levels significantly decreased after immunotherapy.
Conclusion: This study suggests that the chemokine micromilieu, especially the level of CCL18, is different between EAD and IAD patients. High FcεRI surface-expressing DCs, such as IDEC, were the major source of CCL18, and produced a prominent CCL18 microenvironment in EAD patients compared with IAD patients. 相似文献
Objective: We investigated the expression of CC chemokine ligand (CCL) 17, CCL22, and CCL18 in patients with IAD and EAD, which are known to be highly expressed in AD patients.
Methods: We assessed the protein levels of these chemokines in peripheral blood mononuclear cells (PBMCs), sera and lesional skins. We also evaluated CCL18 mRNA levels in monocytes, Langerhans cell (LC)-like dendritic cells (DCs) and inflammatory dendritic epidermal cell (IDEC)-like DCs from both types of AD patients.
Results: There were no significant differences in CCL17 and CCL22 expression in PBMCs, sera and lesional skins of patients with IAD and EAD. CCL18 expression did not differ in PBMCs, sera and LC-like DCs from the two subgroups, but strong CCL18 expression was observed in lesional skins and IDEC-like DCs in patients with EAD. Lastly, serum CCL18 levels significantly decreased after immunotherapy.
Conclusion: This study suggests that the chemokine micromilieu, especially the level of CCL18, is different between EAD and IAD patients. High FcεRI surface-expressing DCs, such as IDEC, were the major source of CCL18, and produced a prominent CCL18 microenvironment in EAD patients compared with IAD patients. 相似文献
7.
L Ma X-H Gao L-P Zhao Z-H Di UO Mchepange L Zhang H-D Chen H-C Wei 《Journal of the European Academy of Dermatology and Venereology》2009,23(11):1277-1281
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. 相似文献
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. 相似文献
8.
Howell MD Novak N Bieber T Pastore S Girolomoni G Boguniewicz M Streib J Wong C Gallo RL Leung DY 《The Journal of investigative dermatology》2005,125(4):738-745
Recurrent skin infections in extrinsic atopic dermatitis (EAD) may be because of the suppression of anti-microbial peptide (AMP) expression by interleukin (IL)-4 and IL-13. Twenty to thirty percent of AD, however, are classified as intrinsic atopic dermatitis (IAD). They exhibit normal serum IgE levels, no allergen-specific sensitization, and lower levels of IL-4 and IL-13 than EAD. Both forms of AD have increased propensity to skin infection, suggesting a novel mechanism for infection in IAD. In this study, we observed significantly decreased human beta-defensin (HBD)-2 gene expression in the skin of both IAD (p = 0.010) and EAD (p = 0.004), as compared with psoriasis patients. Conversely, IAD (p = 0.019) and EAD (p = 0.002) skin lesions exhibited elevated IL-10 gene expression when compared with psoriasis. Using primary keratinocytes, we found that the deficiency in AMP expression is an acquired rather than a constitutive defect. Interestingly, neutralizing antibodies to IL-10 augmented the production of tumor necrosis factor-alpha and interferon-gamma by peripheral blood mononuclear cell from AD patients. Additionally, treatment of AD skin explants with anti-IL-10 augmented the expression of both HBD-2 and LL-37. Thus, increased levels of IL-10 may contribute to the AMP deficiency in both IAD and EAD by reducing cytokines that induce AMP. 相似文献
9.
Lira MG Mazzola S Tessari G Malerba G Ortombina M Naldi L Remuzzi G Boschiero L Forni A Rugiu C Piaserico S Girolomoni G Turco A 《The British journal of dermatology》2007,157(1):49-57
BACKGROUND: Overexpression of cyclooxygenase-2 (COX-2), resulting in excessive prostaglandin production, has been observed in human epidermal keratinocytes after ultraviolet B injury, in squamous cell skin carcinoma (SCC), in actinic keratoses, and in the early stages of carcinogenesis in a wide variety of tissues. The dysregulation of COX-2 expression can in part be due to functional changes affecting regulatory elements in the promoter or 3' untranslated region (UTR) of the gene. Two common polymorphisms (-765G-->C, and -1195A-->G) in the promoter region of the COX-2 gene (now PTGS2), and one common polymorphism in the 3' UTR (8473T-->C) have been described, and reported as associated with various malignancies. OBJECTIVES: To determine if common known polymorphisms in the regulatory region of the COX-2 gene (PTGS2) can be associated with nonmelanoma skin cancer (NMSC) predisposition after organ transplantation, to evaluate if cancer risks are associated with specific COX-2 gene (PTGS2) haplotypes containing these polymorphisms, and to identify possible new genetic polymorphisms in the proximal 5' or 3' regulatory regions of the gene associated with disease. METHODS: The frequency of the three polymorphisms was determined in 240 Northern Italian transplant recipient patients (107 cases and 133 controls) with polymerase chain reaction-restriction fragment length polymorphism analysis. The proximal 5' and 3' regulatory regions of the gene were screened by heteroduplex analysis. RESULTS: Stratification by age at transplant and type of tumours [SCC or basal cell carcinoma (BCC)] demonstrated that allele -765C represented a protective factor in BCC cases undergoing transplantation before 50 years of age (CC + CG vs. GG, Fisher exact test P = 0.003). One rare polymorphism, -62C-->G, was detected in the 5' flanking region. The allele frequency of -62G was 0.019, and no difference in genotype between cases and controls was observed. No other variants were found, suggesting that sequence variations in these regions are not likely to contribute to NMSC risk in this population. Haplotype analysis showed that the haplotype containing all major alleles represents a protective factor in patients with SCC undergoing transplantation after 50 years of age [P = 0.009; OR = 0.37 (0.18-0.79)] and that variant -1195A-->G may represent a risk factor in this subgroup of patients [P = 0.01; OR = 4.77 (1.47-16.41)]. Haplotype analysis in patients with BCC revealed that variant -765C might be a protective factor in patients undergoing transplantation before 50 years of age. Variant 8473T-->C, located in the 3' UTR region of the gene, showed no association with NMSC risk after transplantation. CONCLUSIONS: COX-2 common variants -765G-->C and -1195A-->G appear to be associated with risk of NMSC, although in different ways in the SCC and BCC subgroups, indicating that environmental and genetic risk factors may play different roles in the outcome leading to these two phenotypes. 相似文献
10.
Interleukin-13 gene polymorphism G4257A is associated with atopic dermatitis in Japanese patients 总被引:10,自引:0,他引:10
Tsunemi Y Saeki H Nakamura K Sekiya T Hirai K Kakinuma T Fujita H Asano N Tanida Y Wakugawa M Torii H Tamaki K 《Journal of dermatological science》2002,30(2):100-107
Interleukin (IL)-13 plays an important role in the induction of immunoglobulin E (IgE) and in the pathogenesis of atopic dermatitis (AD). We investigated the allele and genotype frequencies of three IL-13 single nucleotide polymorphisms (SNPs) (A704C and C1103T in the promoter region and G4257A in exon 4) in Japanese patients with AD. For A704C and C1103T SNPs, there were no significant differences in allele or genotype frequencies between AD patients and controls. For G4257A SNP, A allele was significantly increased in AD patients (39.5%) compared with controls (29.4%) (P = 0.016). The same proportion of each genotype and allele was observed in the patient subgroup with and without asthma. Serum IgE levels and peripheral eosinophil counts were not significantly different among genotypes in G4257A SNP. There was also no significant difference in allele or genotype frequencies between AD patients with mild disease and those with severe disease, between those with family history of AD and those without it, or between those with family history of atopic disorders and those without it. This result suggests that 4257A allele is associated with susceptibility to AD and that it may function in the pathogenesis of AD itself, presumably by other mechanisms than inducing IgE production. 相似文献
11.
Moises-Alfaro CB Caceres-Rios HW Rueda M Velazquez-Acosta A Ruiz-Maldonado R 《International journal of dermatology》2002,41(6):349-351
BACKGROUND: The relationship between infantile seborrheic dermatitis (ISD) and infantile atopic dermatitis (IAD) is controversial. METHODS: Ninety-six children aged 2-12 months diagnosed with atopic dermatitis and a comparable control group of healthy children were evaluated. Demographic data, personal history of ISD and personal or family history of atopy was considered in both groups. RESULTS: A personal history of ISD was found in 49% of IAD cases and in 17% of controls (P < 0.05). CONCLUSIONS: Our result and those of the literature do not demonstrate a relationship between ISD and IAD. However, a number of cases of AD have an ISD-like clinical picture. It is probable that ISD is a syndrome and not a disease. 相似文献
12.
Microsatellite instability and reduced expression of mismatch repair proteins were reported in melanomas. However, little is known about mutational changes of the mismatch repair genes in radial growth-phase melanoma especially following UVB irradiation. To investigate these changes, an in vitro system consisting of radial growth-phase Wistar melanoma cell lines (WM35, WM3211 and WM1650) was established. The cells were UVB irradiated (10 mJ/cm(2)), and evaluated for mutational changes of exon regions 13,16 and 19 (hMLH1) and 6,7 and 12 (hMLH2) of these genes before and after irradiation. The genomic DNAs were PCR amplified and the products were directly sequenced. Transition (C-->T, G-->A, T-->C) and transversion (G-->, A-->T) mutations were found in exons 6,16 and 19. Some were present in both the sham-irradiated and UV-irradiated cells but others were only detected after UVB irradiation. hMLH1 and hMLH2 gene mutations occur early in melanoma tumorigenesis. The ability of UVB irradiation to induce additional mutations in these repair genes suggests its possible role in melanoma pathogenesis. Further investigation will be needed to determine whether mutations such as these contribute to the development of microsatellite instability in melanoma. 相似文献
13.
Tsuyoshi Yatagai Takatoshi Shimauchi Hayato Yamaguchi Jun-ichi Sakabe Masahiro Aoshima Shigeki Ikeya Kazuki Tatsuno Toshiharu Fujiyama Taisuke Ito Toshiyuki Ojima Yoshiki Tokura 《Journal of dermatological science》2018,89(1):33-39
Background
Sensitive skin is a condition of cutaneous hypersensitivity to environmental factors. Lactic acid stinging test (LAST) is commonly used to assess sensitive skin and composed of four distinct sensations (pain, burning sensation, itch, and crawly feeling). A link between sensitive skin and barrier dysfunction has been proposed in atopic dermatitis (AD) patients. However, clinical and laboratory factors that are associated with sensitive skin remain unelucidated.Objective
To investigate relationship between sensitive skin and AD-associated markers.Methods
Forty-two Japanese AD patients and 10 healthy subjects (HS) were enrolled. AD patients were divided into extrinsic (EAD; high IgE levels) and intrinsic (IAD; normal IgE levels) types. We conducted 1% LAST by assessing the four distinct sensations and calculated the frequencies of sensitive skin in EAD, IAD, and HS. We also performed clinical AD-related tests, including transepidermal water loss (TEWL), visual analogue scale (VAS) of pruritus, and quality of life, and measured laboratory markers, including blood levels of IgE, CCL17/TARC, lactate dehydrogenase (LDH) and eosinophil counts, and concentration levels of serum Th1/Th2 cytokines. Filaggrin (FLG) mutations were examined in 21 patients. These values were subjected to correlation analyses with each of the four sensation elements.Results
According to the standard criteria for LAST positivity, the frequencies of LAST-positive subjects were 54.8% and 10.0% in AD and HS, respectively (P = 0.014). EAD patients showed a significantly (P = 0.026) higher frequency of positive LAST (65.6%) than did IAD patients (20.0%). Among the four LAST sensation elements, the crawly feeling and pain scores positively correlated with VAS of pruritus, total serum IgE, mite-specific IgE, CCL17/TARC, and/or LDH. There was no association of the LAST scores with serum Th1/Th2 cytokine levels. Notably, neither TEWL nor FLG mutations correlated with LAST positivity or any sensation scores.Conclusions
The frequency of sensitive skin is higher in EAD than in IAD. Sensitive skin is associated with AD severity, but not necessarily with barrier condition. 相似文献14.
Germline mutations in PTEN, a putative tumor suppressor gene, has been identified in 2 autosomal dominant inherited hamartoma syndromes, Cowden syndrome (CS) and Bannayan-Zonana syndrome (BZS). While both diseases exhibit distinct phenotypic features, there seems to be a partial clinical overlap between the 2 diseases. To date, 9 families with BZS have been screened for PTEN mutations, of which 5 were found to exhibit mutations in this gene. We report 5 novel germline mutations in the PTEN coding sequence from 5 unrelated families with the BZS phenotype. While all the mutations we identified are novel in BZS, 1003C-->T (nonsense mutation) and 209+5G-->A (putative splice site mutation) have been previously reported in unrelated families with CS and Lhermitte Duclos disease. Interestingly, 1 of the families has an individual with BZS and 1 with CS phenotype, associated with a single PTEN mutation, 885insA. These data support the notion that CS and BZS may be within the spectrum of the same primary disorder. 相似文献
15.
Morar N Cookson WO Harper JI Moffatt MF 《The Journal of investigative dermatology》2007,127(7):1667-1672
Atopic dermatitis (AD) results from strong genetic and environmental interactions. AD shows genetic linkage to Chromosome 1q21. This region contains the epidermal differentiation complex (EDC), which consists of genes that form essential components of epidermal surfaces. Filaggrin (FLG) is one of these. Mutations in FLG/(R501X and 2282del4) are reported to be strongly associated with AD and to influence asthma accompanying AD. We investigated these effects in families recruited through a child with severe AD. We genotyped two panels of families, totalling 426, containing 990 affected and unaffected children. We found significant associations with AD (P=0.0001), asthma (P=0.006), and atopy (P=0.002). The FLG mutations were present in 26.7% of patients with AD, but were also present in 14.4% of children without AD. They were weakly associated with disease severity. The variants were not independently associated with asthma. The overall LOD score for genetic linkage of markers to the region was 3.57. This fell to 2.03 after accounting for the FLG mutations, indicating the presence of other genetic variants influencing AD at this locus. Our results provide further confirmation of the importance of mutations in FLG and the skin barrier in AD pathogenesis. The results indicate that investigations of other genes within the EDC should be undertaken. 相似文献
16.
目的:检测窄谱中波紫外线(NB-UVB)联合吡美莫司乳膏治疗前后,特应性皮炎 (AD) 患者外周血嗜酸性粒细胞活化趋化因子(eotaxin)与其相应受体CCR3的表达,以探讨其治疗特应性皮炎的相关机制。方法: 采用窄谱中波紫外线联合吡美莫司乳膏治疗30例成人型AD患者,酶联免疫吸附试验检测治疗前后血清中eotaxin水平; 同时用流式细胞仪分析外周血中CCR3的表达。结果: 治疗前,AD患者血清eotaxin水平为(133.86±42.23) pg/mL,CCR3表达水平为(23.10±6.31)%;治疗后,AD患者血清eotaxin水平为(101.54±35.63) pg/mL,较治疗前明显降低(t=3.20,P<0.01);外周血 CCR3表达水平为(16.52±6.59)%,较治疗前亦明显降低(t=3.59,P<0.01)。结论: 窄谱中波紫外线联合吡美莫司乳膏可能通过降低eotaxin、CCR3表达,从而减少嗜酸性粒细胞的募集、活化,发挥其治疗特应性皮炎的作用。 相似文献
17.
目的 探讨中间丝聚合蛋白(FLG)基因多态性与特应性皮炎(AD)发病及临床表型的相关性.方法 采用问卷调查的形式收集261例AD患者伴发过敏性鼻炎、哮喘病史和疾病严重度评分等资料,对部分患者进行混合食物过敏原和混合吸人性过敏原筛选、血清总IgE抗体和嗜酸性粒细胞阳离子蛋白水平检测.采用重叠PCR和DNA测序法对上述AD患者和276例健康对照FLG基因3号外显子17个多态性位点(R444G、T454A、P478S、H519N、D836D、S1482Y、A1805V、R1891Q、1961Q、S2166S、Y2194H、H2330H、D2339N、S2366T、E2398Q、K2444E、E2652D)进行基因分型.结果 二项逻辑回归分析和卡方检验未发现17种FLG多态位点与AD发病相关(均P>0.05).H519N与AD伴发哮喘相关(x2=8.680,P=0.011),AA基因型可增加AD患者发生哮喘的风险(P=0.004,OR=1.061,95% CI 1.016 ~ 1.109).S2366T和K2444E与AD患者食物敏感相关(x2值分别为6.520和6.121,P值分别为0.038和0.047),S2366T的GG+ GC基因型(P=0.012,OR=1.396,95%CI 1.054~1.849)和G等位基因(P=0.037,OR=1.350,95%CI 1.008~ 1.807)可提高AD患者食物敏感的风险.K2444E的AA+ AG基因型(P=0.013,OR=1.393,95% CI 1.049 ~ 1.850)和G等位基因(P=0.028,OR=1.380,95% CI 1.025 ~ 1.857)可提高AD患者食物敏感的风险.结论 中国汉族人群FLG基因多态性可能是一些AD相关临床表型的危险因素,H519N可能与AD伴发哮喘相关,S2366T和K2444E则可能与AD伴食物敏感相关. 相似文献
18.
目的 了解深圳市1~7岁儿童特应性皮炎(AD)的患病情况及影响因素,分析不同标准诊断结果差异.方法 2013年12月1日至2014年3月1日采用问卷与体检相结合的方式调查深圳市1~7岁儿童AD的患病情况.结果 共纳入1 504名儿童,其中男716例、女788例.以有经验皮肤科医生的临床诊断为标准,AD总患病率为11.84%(178例),男性患病率为11.73%(84例),女性为11.93% (94例).男性与女性患病率差异无统计学意义(x2=0.01,P>0.05).基于Williams诊断标准,AD总患病率为3.92%(59例),男性患病率为4.05%(29例),女性为3.81%(30例).早产是AD发病的危险因素(x2=5.43,P< 0.05).结论 深圳市1~7岁儿童AD患病率明显上升,早产是AD的危险因素;以有经验皮肤科医生的临床诊断作为标准可以减少AD漏诊. 相似文献
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【摘要】 目的 探讨Th17细胞和Treg细胞失衡在特应性皮炎(AD)发病机制中的作用。方法 流式细胞仪检测52例AD患者外周血Th17细胞和Treg细胞的频率、酶联免疫吸附方法(ELISA) 检测外周血中细胞因子IL-6、TGF-β1的表达水平。同时以30例性别、年龄匹配的健康体检者作为对照。结果 AD组外周血Th17细胞(CD3+CD8-IL17+)占CD3+T细胞的百分比为(1.20 ± 0.41)%,高于对照组的(0.54 ± 0.28)% (t = 2.58,P < 0.05);Treg(CD4+ CD25+)细胞的百分比为(2.29 ± 0.67)%,低于对照组(5.95 ± 0.45)%,(t = 15.23,P < 0.01)。关键调控因子测定结果:IL-6水平,AD组(5.12 ± 0.45)ng/L高于对照组(3.89 ± 0.38) ng/L,差异具有统计学意义(t = 2.59,P < 0.05);而TGF-β1的表达水平AD组(57.65 ± 10.78) ng/L低于对照组的(81.18 ± 7.78) ng/L,(t = 5.41,P < 0.01)。 结论 特应性皮炎患儿外周血Th17、Treg细胞水平及其关键的调控平衡因子IL-6、TGF-β1发生变化,其比例的失平衡可能参与特应性皮炎的发病。 相似文献
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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。 相似文献