Department of Dermatovenereology, University Medical Centre Ljubljana, Ljubljana, Slovenia; Dermatology Centre Arsderma, Ljubljana, Slovenia.
Br J Dermatol. 2015 Feb;172(2):455-61. doi: 10.1111/bjd.13477. Epub 2015 Jan 6.
The influence of filaggrin gene (FLG) mutations on early- vs. late-onset development of atopic dermatitis (AD), allergic contact dermatitis (ACD) and chronic irritant contact dermatitis (CICD) is not completely understood.
To assess the association between FLG mutations and development of AD, ACD and CICD.
This study assessed 241 patients with AD. AD developed during infancy in 85 patients, during childhood in 79 patients (32 early and 47 late) and during adulthood in 77 patients. We also included 100 patients with ACD and 44 with CICD, as well as 164 healthy controls. Four prevalent FLG loss-of-function mutations were genotyped (R501X, 2282del4, R2447X and S3247X).
The 2282del4 mutation was significantly associated with a greater risk of AD in the entire group [odds ratio (OR) 4·33, 95% confidence interval (CI) 1·26-14·96]. However, the 2282del4 mutation was associated only with AD that developed during infancy or in early childhood (≤ 8 years: OR 20·91, 95% CI 2·73-159·9), not with AD development in late childhood or adulthood (> 8 or > 18 years), or ACD or CICD. Similar associations were also observed for the combined 2282del4 or R501X genotype. Carriers of FLG mutations also experienced a longer duration of AD and required hospitalization more often.
FLG mutations are associated with only the early onset of AD, not late onset. Other factors should receive attention in patients with late-onset AD.
丝聚蛋白基因（FLG）突变对特应性皮炎（AD）、变应性接触性皮炎（ACD）和慢性刺激性接触性皮炎（CICD）的早发和晚发的影响尚不完全清楚。
评估 FLG 突变与 AD、ACD 和 CICD 发展之间的关联。
本研究评估了 241 例 AD 患者。85 例患者的 AD 在婴儿期发病，79 例（32 例早发，47 例晚发）在儿童期发病，77 例在成年期发病。我们还纳入了 100 例 ACD 患者和 44 例 CICD 患者，以及 164 例健康对照者。对 4 种常见的 FLG 功能丧失突变（R501X、2282del4、R2447X 和 S3247X）进行了基因分型。
2282del4 突变与整组患者发生 AD 的风险显著增加相关（比值比[OR] 4.33，95%置信区间[CI] 1.26-14.96）。然而，2282del4 突变仅与婴儿期或儿童早期（≤8 岁：OR 20.91，95%CI 2.73-159.9）发生的 AD 相关，与儿童后期或成年期（>8 岁或>18 岁）发生的 AD 或 ACD 或 CICD 无关。联合 2282del4 或 R501X 基因型也观察到类似的关联。FLG 突变携带者还经历了更长时间的 AD 病程，更频繁需要住院治疗。
FLG 突变仅与 AD 的早发有关，而与晚发无关。对于晚发 AD 患者，应关注其他因素。
