Filaggrin null mutations are associated with atopic dermatitis and elevated levels of IgE in the Japanese population: a family and case-control study
Filaggrin null mutations are associated with atopic dermatitis and elevated levels of IgE in the Japanese population: a family and case-control study
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DOI：
10.1007/s10038-008-0293-z
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发表时间：
2008-07-01
影响因子：
3.5
通讯作者：
Noguchi, Emiko
中科院分区：
文献类型：
--
作者：
Enomoto, Hisako;Hirata, Kenji;Noguchi, Emiko
聚丝蛋白（Filaggrin，FLG）在皮肤屏障功能中起重要作用。在寻常型鱼鳞病患者中发现了FLG基因的几种功能缺失突变，这些无效突变与特应性皮炎（AD）的发生有关。在这项研究中，我们研究了标签单核苷酸多态性（tSNPs）和无效突变FLG可能与AD和特应性表型在日本人口。对105个AD家系的传递不平衡检验显示，FLG基因S2554X变异体的无效等位基因有向AD患者后代过度传递的趋势，但P值未达到统计学意义。在376例AD患者和923例非过敏对照的病例对照比较中，S2554X的无效等位基因与AD显著相关（P = 0.0012），并且在单独AD患者中这种相关性得到加强（P = 0.000024）。我们发现3321delA和S2554X也与免疫球蛋白E（IgE）水平升高相关。AD患者和高IgE受试者中观察到的联合无效突变携带者多于对照受试者。对于S2554X和组合无效突变，家族和病例对照数据的组合P值是显著的。我们的数据进一步支持FLG在AD发展中的重要性。
Filaggrin (FLG) plays an important role in the barrier function of the skin. Several loss-of-function mutations in the FLG gene have been identified in patients with ichthyosis vulgaris, and these null mutations are associated with atopic dermatitis (AD) development. In this study, we examined tag single nucleotide polymorphisms (tSNPs) and null mutations in FLG for possible associations with AD and atopic phenotypes in a Japanese population. Transmission disequilibrium test of 105 AD families showed that the null allele of the S2554X variant of FLG tended to be overtransmitted to AD-affected offspring; however, the P value did not reach statistical significance. In a case-control comparison of 376 AD cases and 923 nonallergic controls, the null allele of S2554X was significantly associated with AD (P = 0.0012), and the association was strengthened in subjects with AD alone (P = 0.000024). We found that 3321delA and S2554X were also associated with elevated levels of immunoglobulin E (IgE). Combined null mutation carriers were observed more in AD patients and in subjects with high IgE than in control subjects. The combined P value for the family and case-control data was significant for the S2554X and combined null mutations. Our data further support the importance of FLG in AD development.