Weidinger S, Klopp N, Rümmler L, Wagenpfeil S, Baurecht H J, Gauger A, Darsow U, Jakob T, Novak N, Schäfer T, Heinrich J, Behrendt H, Wichmann H E, Ring J, Illig T
Department of Dermatology and Allergy Biederstein, Technical University Munich, Germany.
Clin Exp Allergy. 2005 Jul;35(7):866-72. doi: 10.1111/j.1365-2222.2005.02269.x.
Influences of microbial pathogens are crucial for the maturation of the immune system. Caspase-recruitment domain containing protein 15 (CARD15) is a cytosolic receptor involved in bacterial recognition by antigen-presenting cells. CARD15 polymorphisms have been associated with Crohn's disease. Recently, associations with atopic phenotypes have been reported in children.
Within a large population of German adults (n=1875), we evaluated eight CARD15 polymorphisms for associations with atopic phenotypes.
Subjects were phenotyped by standardized questionnaires and interviews as well as total and allergen-specific IgE measurements. Genotyping was performed using matrix-assisted laser desorption ionization--time of flight mass spectrometry. Haplotypes were estimated using the SAS/Genetics module.
Subjects with a T allele at rs1077861 had a decreased risk of developing asthma (odds ratio OR=0.648, P=0.013), whereas the presence of an A allele at rs3135500 was significantly associated with an increased risk (OR=1.374, P=0.023). In addition, a CARD15 haplotype revealed to be protective against the development of asthma (OR=0.326, P=0.003). Subjects with an A allele at position rs5743266 or a T allele at rs2066842 had a significantly decreased risk of developing allergic rhinoconjunctivitis with ORs of 0.820 (P=0.049) and 0.801 (P=0.025). Polymorphism rs2066845 showed a significant association with increased total serum IgE (OR=2.155, P=0.006).
Genetic variants of CARD15 that might result in inappropriate immunomodulation are not only associated with autoimmune diseases but also with atopic disorders.
微生物病原体的影响对免疫系统的成熟至关重要。含半胱天冬酶招募结构域蛋白15（CARD15）是一种胞质受体，参与抗原呈递细胞对细菌的识别。CARD15基因多态性与克罗恩病有关。最近，有报道称儿童中存在与特应性表型的关联。
在一大群德国成年人（n = 1875）中，我们评估了8种CARD15基因多态性与特应性表型的关联。
通过标准化问卷、访谈以及总IgE和变应原特异性IgE测量对受试者进行表型分析。使用基质辅助激光解吸电离飞行时间质谱进行基因分型。使用SAS/Genetics模块估计单倍型。
rs1077861位点有T等位基因的受试者患哮喘的风险降低（优势比OR = 0.648，P = 0.013），而rs3135500位点存在A等位基因与风险增加显著相关（OR = 1.374，P = 0.023）。此外，一种CARD15单倍型显示对哮喘的发生有保护作用（OR = 0.326，P = 0.003）。rs5743266位点有A等位基因或rs2066842位点有T等位基因的受试者患变应性鼻结膜炎的风险显著降低，优势比分别为0.820（P = 0.049）和0.801（P = 0.025）。多态性rs2066845与血清总IgE升高显著相关（OR = 2.155，P = 0.006）。
可能导致免疫调节不当的CARD15基因变异不仅与自身免疫性疾病有关，还与特应性疾病有关。
