上海某中学青少年特应性皮炎和鱼鳞病FLG基因型的研究

Prevalence of atopic dermatitis, ichthyosis and filaggrin mutations in adolescents in a middle school in Shanghai

目的探讨青少年FLG基因型、了解特应性疾病患病率、发展进程及其FLG基因的关系。方法上海某中学334例11—19岁青少年作为研究样本，进行鱼鳞病、特应性皮炎（AD）、哮喘、鼻炎等特应性疾病的临床病史及体征观察、记录。285例进行了外周血采样及FLG基因高频突变筛查。5年后，进行样本人群随访，观察并记录各特应性疾病的临床症状及体征。结果5年前，334例青少年中AD19例（5．69％），寻常性鱼鳞病14例（4．19％），过敏性鼻炎36例（10．78％），哮喘4例（1．20％）。在完成FLG基因测序的285例样本中，携带FLG基因高频突变者24例（8．42％）。5年后完成随访265例，失访69例（20．66％），AD、鱼鳞病、过敏性鼻炎及哮喘的患病人数分别为13例（4．89％）、15例（5．64％）、27例（10．15％）、1例（0．38％），原19例AD中6例进入完全缓解期，13例SCORAD评分明显下降，原36例过敏性鼻炎中9例症状消失。单纯AD、单纯鱼鳞病、AD合并鱼鳞病的FLG基因高频突变率分别为10．0％、55．6％、40．0％，且患鱼鳞病与FLG基因突变有关（P〈0．001）。结论青少年中，FLG基因高频突变率为8．42％。FLG基因是寻常性鱼鳞病的半显性遗传因素，中间丝聚合蛋白的表达受多因素影响。

Objective To investigate the prevalence and progression process of atopic diseases in adolescents, and to assess their relationship with filaggrin （FLG） mutations. Methods Totally, 334 adolescents aged from 11 to 19 years in a middle school in shanghai were enrolled into this study. A clinical interview was carried out to determine the prevalence of atopic diseases （such as ichthyosis, atopic dermatitis （AD）, asthma, rhinitis, etc） in these subjects. Peripheral blood samples were collected from 285 out of the 334 adolescents for screening for common FLG mutations, including 3321delA and K4671X. Five years later, these adolescents were followed up for reevaluation of clinical presentations of atopic diseases. Statistical analysis was carried out by the chi-square test with the SPSS 20.0 software. Results As the baseline survey showed, 19 （5.69%） of the 334 adolescents had AD, 14 （4.19%） had ichthyosis vulgaris, 36 （ 10.78% ） had allergic rhinitis, and 4 （ 1.20% ） had asthma. FLG mutations were observed in 24 （ 8.42% ） of the 285 adolescents. Five years later, 265 adoscents completed the follow-up, and 69 （20.66%） were lost to followup. Of the 265 adolescents reevaluated, 13 （4.89%） had AD, 15 （5.64%） had ichthyosis vulgaris, 27 （10.15%） had allergic rhinitis, and 1 （0.38%） had asthma. By the time the second survey was performed, 6 out of the 19 patients initially diagnosed with AD had achieved complete regression, 13 had experienced a marked decrease in SCORing atopic dermatitis （SCORAD） score, and symptoms had disappeared in 9 of the 36 patients initially diagnosed with allergic rhinitis. The frequency of FLG mutations was 10.0% in patients with AD, 55.6% in those with ichthyosis, and 40.0% in those with both AD and ichthyosis, and the development of ichthyosis was associated with FLG mutations （ P 〈 0.001 ）. Conclusions The frequency of common FLG mutations was 8.42% in these adolescents. FLG gene may be a semidominant gene associated with ichthyosis vulgaris, and multiple factors influence its expression.