المؤلفون: Weidinger, Stephan, Baurecht, Hansjörg, Wagenpfeil, Stefan, Henderson, John, Novak, Natalija, Sandilands, Aileen, Chen, Huijia, Rodriguez, Elke, O'Regan, Grainne M., Watson, Rosemarie, Liao, Haihui, Zhao, Yiwei, Barker, Jonathan N.W.N., Allen, Michael, Reynolds, Nick, Meggitt, Simon, Northstone, Kate, Smith, George D., Strobl, Carolin, Stahl, Caroline

المصدر: Journal of Allergy & Clinical Immunology; Sep2008, Vol. 122 Issue 3, p560-568, 9p

مصطلحات موضوعية: SERINE proteinase inhibitors, PEPTIDASE, GENETIC polymorphisms, ECZEMA -- Risk factors, KALLIKREIN, HUMAN genetics, COHORT analysis

مستخلص: Background: Polymorphisms in the serine protease inhibitor gene serine peptidase inhibitor Kazal type 5 (SPINK5) and the serine protease kallikrein-related peptidase 7 gene (KLK7) appear to confer risk to eczema in some cohorts, but these findings have not been widely replicated. These genes encode proteins thought to be involved in the regulation of posttranslation processing of filaggrin (FLG), the strongest identified genetic risk factor for eczema to date. Objectives: We sought to clarify the individual risk of eczema conferred by the SPINK5 polymorphism rs2303067 (Glu420Lys) and a previously described insertion in the 3′ untranslated region of KLK7 and to examine potential epistatic effects between these variants and FLG mutations. Methods: Initially, we examined the effects of these polymorphisms and FLG in 486 unrelated patients from a German family-based study, an additional 287 German patients, and 418 unrelated Irish/English patients with eczema (n for 3 genes studied = 1191 vs 4544 control subjects). We then additionally studied the SPINK5 polymorphism and FLG mutations in 1583 patients with eczema from the Avon Longitudinal Study of Parents and Children cohort (sample size for 2 genes studied = 2774 vs 10,607 control subjects). Results: No association was seen with the SPINK5 or KLK7 variants in the case-control analysis; however, a weaker effect was observed for the SPINK5 variant with maternal transmission in the family-based study. No interactions were seen between the polymorphisms in KLK7, SPINK5, and FLG. Conclusion: The SPINK5 420LysSer mutation confers a risk of eczema when maternally inherited but is not a major eczema risk factor. The KLK7 insertion appears to confer no risk of eczema. We found no interaction between the SPINK5 risk allele or the putative KLK7 risk allele and FLG mutations. [Copyright &y& Elsevier]

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المؤلفون: Skov, Lone, Allen, Michael H., Bang, Bo, Francis, David, Barker, Jonathan N.W.N., Baadsgaard, Ole

المصدر: Experimental Dermatology; Dec2003, Vol. 12 Issue 6, p772-776, 5p

مصطلحات موضوعية: BASAL cell carcinoma, TUMOR necrosis factors, ULTRAVIOLET radiation, GENETIC polymorphisms, SKIN cancer, GROWTH factors

مستخلص: Skov L, Allen MH, Bang B, Francis D, Barker JNWN, Baadsgaard O. Basal cell carcinoma is associated with high TNF-α release but not with TNF-α polymorphism at position − 308. The mechanisms underlying induction of UVB-induced immunosuppression are not fully understood, but tumour necrosis factor alpha (TNF-α) is suggested to play a central role. A single base pair polymorphism at position − 308 in the promoter region of the TNF-α gene associated with an enhanced secretion of TNF-α has been identified in humans. We have therefore investigated the association of the − 308 polymorphism with the risk of basal cell carcinoma (BCC) in humans. The frequency of TNF G and TNF A alleles among Caucasian patients with a previous BCC ( n= 191) and healthy adults ( n= 107) were compared. For the TNF − 308 polymorphism there was no significant association between the genotype or allele frequencies and having a BCC. To determine whether patients with a previous BCC had an increased capacity to secrete TNF-α, mononuclear cells were stimulated with lipopolysaccharide. Mononuclear cells from patients with a previous BCC ( n= 15) demonstrated a significantly increased release of TNF-α upon stimulation with lipopolysaccharide ( P < 0.03) compared with mononuclear cells from age-matched control subjects ( n= 16). Further studies of other polymorphisms of the TNF-α gene associated with increased TNF-α production and BCC are necessary. [ABSTRACT FROM AUTHOR]

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المؤلفون: Allen, Michael H., Wakelin, Sarah H., Holloway, Doris, Lisby, Steen, Baadsgaard, Ole, Barker, Jonathan N.W.N., McFadden, John P.

المصدر: Immunogenetics; Mar2000, Vol. 51 Issue 3, p201-205, 5p

مصطلحات موضوعية: CYTOKINES, GENETIC polymorphisms, GENES, GROWTH factors, TUMOR necrosis factors, IMMUNOREGULATION, CONTACT dermatitis

مستخلص: Mechanisms underlying susceptibility to skin irritants are not clearly understood. Cytokines play a key role in inflammation, and functional polymorphisms in cytokine genes may affect responses to irritants. We investigated the relationship between polymorphism in the tumor necrosis factor (TNF) α-chain gene and responses to irritants. Volunteers (n=221) tested with sodium dodecyl sulfate (SDS) and benzalkonium chloride (BKC) were divided into responders and nonresponders and high and low irritant-threshold groups. DNA was assayed for the TNF-308 polymorphism by a polymerase chain reaction-restriction fragment length polymorphism method. There was a significant increase in the A allele (P=0.030) and AA genotype (P=0.023) in both the SDS low irritant-threshold group and in SDS responders (A allele P=0.022, AA genotype P=0.048). In the BKC low irritant-threshold group, we found a significant increase in the A allele (P=0.002) and AA genotype (P=0.016). Individuals with a low threshold to both irritants demonstrated a significant increase (P=0.002) in the A allele. This is the first description of a nonatopic genetic marker for irritant susceptibility in normal individuals. Genotyping for theTNF-308 polymorphism may thus contribute to screening of individuals deemed at risk of developing irritant contact dermatitis. [ABSTRACT FROM AUTHOR]

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