淺談纖聚蛋白（filaggrin）與異位性皮膚炎

Filaggrin Gene Defects and Atopic Dermatitis

異位性皮膚炎(atopic dermatitis；AD)為一種慢性反覆的疾病，好發於嬰兒期與兒童期，為常見的角質化缺失疾病，特徵是皮膚乾燥脫屑及表現過敏性皮膚症狀。纖聚蛋白filaggrin (FLG)基因突變與AD、氣喘、過敏性鼻炎(allergic rhinitis)都具高度的關聯性。其中尋常性魚鱗癬症為FLG基因突變，造成filaggrin蛋白缺乏所引起。Filaggrin是表皮keratohyalin granules cell的主要成份，其基因位於chromosome 1q21.3，含有3個exon，分別是exon 1、exon 2與exon 3。其中exon 3主要由10，11或12個序列幾乎完全相同的短片段序列(tandem repeats)所組成，其總長約12.39 kb。根據報導，和AD相關的FLG熱門突變點都位於exon 3，因此要建立FLG mutations的基因檢測系統並不容易。根據長庚醫院2002年的調查統計，異位性皮膚炎在6~7歲的盛行率約10.6%，13~14歲為7.4%。目前只能間接檢測血清中IgE level是否升高，或是做相關的過敏原檢查，尚未有直接的檢驗方法來診斷異位性皮膚炎，只能就臨床症狀與病史做綜合診斷。我們期望在不久的將來能發展出低成本且快速的Filaggrin基因診斷方法，幫助臨床醫師在表皮屏障功能治療上的策略決定，或是做為AD的預防性診斷。

Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Mutations in the gene encoding filaggrin (FLG) have been identified as the cause of ichthyosis vulgaris (IV) and the major predisposing factors for atopic dermatitis (AD). In addition, FLG mutations are significantly associated with AD-associated asthma and allergic rhinitis. In terminally differentiated keratinocytes, filaggrin is crosslinked to the cornified cell envelope, which constitutes an insoluble barrier in the stratum corneum, protecting the organism against environmental agents and preventing epidermal water loss. The filaggrin gene resides on chromosome 1q21 and consists of three exons. Among these, exon 3 is extremely large (>12 kb) and encodes most of the profilaggrin polypeptides with almost identical 10, 11 or 12 tandem repeat units. Direct sequencing of exon 3 is thus difficult. According to the epidemiology study of AD from Chang Gang memorial hospital, the prevalence of AD in children of 6~7 years old is about 10.6%, and 7.4% in children of 13~14 years old. Currently there is no available molecular diagnostic method for AD in clinic practice. However, in the near future, we might envise using inexpensive and rapid genetic testing for filaggrin mutations. This may be coupled with an appropriate treatment regimen designed to enhance the barrier function of the skin. An early preventive measure for persons at risk for atopic dermatitis may be developed.