異位性皮膚炎聚角蛋白微絲基因之新生兒篩檢與遺傳諮詢

Abstract

異位性皮膚炎（Atopic Dermatitis, AD）依過往文獻統計，全球總體盛行率約9.6%-20%，根據台灣健保資料庫（NHI）2000年至2007年的統計，國人盛行率約6.7%。造成此疾病的最大原因，據以往研究顯示有約70%-85%為聚角蛋白微絲基因（Filaggrin gene, FLG gene）變異所引起，此基因變異會導致皮膚屏障（Skin barrier）功能缺損，保濕能力下降，進一步引發過敏原侵入，使得免疫功能失調，造成異位性皮膚炎發生。 現行檢測與病程發展，是患者臨床症狀嚴重進而尋求專業醫師協助，後續透過臨床診斷並給予治療與用藥；如能在疾病誘發前進行基因檢測，並在衛教諮詢與專業醫師協助下提早預防勝於治療，本次研究將透過追蹤統計進一步探討，諮詢衛教的介入降低異位性皮膚炎被誘發的可能性；並藉此統計台灣盛行率建立資料庫與高低風險族群比例，基因型與臨床症狀的關聯性，並透過基因找出台灣族群的常見點位。 本次研究依據過去國內外文獻所提及之FLG基因突變點位，從中挑選20個突變點位進行實驗，收案時間2015年至2020年03月份共8,076個新生兒；透過研究結果顯示，台灣異位性皮膚炎新生兒患者有65.8%為FLG基因異常，而台灣族群的盛行率為39.3%，透過檢測得知前三名常見點位分別是c.1432C>T/c.1432C>T佔79.4%、c.12064A>T佔9.7%、以及c.3321delA佔6.6%，後續透過衛教諮詢的介入之下，降低63.3%新生兒成為異位性皮膚炎患者。 此研究得知，透過基因檢測、臨床診斷、衛教諮詢，可降低異位性皮膚炎發病率，也讓未來高風險族群之新生兒把傷害降到最低。

According to the statistics from previous studies, the global prevalence of atopic dermatitis (AD) is around 9.6% to 20%. The statistics drawn from Taiwan’s National Health Insurance (NHI) Database revealed that the prevalence of AD in Taiwan was 6.7% from 2000 to 2007. With regard to the primary cause of the disease, previous studies have demonstrated that 70% to 85% of cases are caused by mutations of the filaggrin (FLG) gene. Such mutations result in skin barrier dysfunction and reduced water-holding capacity, thereby exposing the skin to allergens and causing immunity system disorders and AD. With respect to the testing and course of AD, current standards call for patients with serious clinical symptoms to seek professional assistance from physicians and receive treatment and medications based on their clinical diagnosis results. AD can be prevented if genetic testing is performed before the onset of the disease and assistance is provided through health consultations and physician visits. This study aimed to explore the possibility of reducing the likelihood of the onset of AD by tracking the statistics of AD and implementing health consultation interventions. In so doing, the statistical data can be used to establish a database covering the prevalence of AD in Taiwan and the percentage of high-risk groups, uncover the association between genotypes and clinical symptoms, and determine the common points of mutations among ethnic groups in Taiwan. 20 points of FLG mutations reported in local and overseas studies were selected for the experiments performed in this study. The participants were 8,076 neonates enrolled from 2015 to March 2020. The results demonstrated that 65.8% of the neonates in Taiwan had FLG gene abnormalities, while the prevalence of AD in Taiwan was 39.3%. The test results showed that the three most common points of mutation were c.1432C>T/c.1432C>T (which accounted for 79.4%), c.12064A>T (9.7%), and c.3321delA (6.6%). By means of subsequent health consultation interventions, AD was reduced among 63.3% of the neonates. Based on the results of this study, genetic testing, clinical diagnosis, and health consultation are effective means for reducing the incidence of atopic dermatitis and for minimizing injuries among high-risk neonates.