University Department of Growth and Reproduction, Copenhagen University Hospital Rigshospitalet, Section 5064, Blegdamsvej 9, 2100 Copenhagen, Denmark.
University Department of Growth and Reproduction, Copenhagen University Hospital Rigshospitalet, Section 5064, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Environ Int. 2017 Aug;105:105-111. doi: 10.1016/j.envint.2017.05.013. Epub 2017 May 17.
Filaggrin is an epidermal protein that is important for normal skin barrier functions. Up to 10% of Europeans and Asians carry filaggrin gene (FLG) loss-of function mutations that appear to facilitate trans-epidermal penetration of certain chemicals. We previously showed that mutation carriers have higher internal exposure to certain phthalates, compared to controls, and hypothesized that they could have increased trans-epidermal penetration of other chemicals.
We investigated exposure to non-persistent chemicals in young Danish men with and without FLG mutations.
Concentrations of eight simple phenols, six parabens and nine UV filters were analysed in urine from 65 FLG loss-of-function mutation carriers and 130 non-carriers (controls). Regression analyses, controlling for urinary dilution and confounders, were performed to estimate associations between FLG mutation status and chemical concentrations in urine.
FLG mutation carriers had 80% (13-180%) higher urinary concentrations of methyl paraben (MeP) and 91% (13-219%) higher concentrations of n-propyl paraben (n-PrP) than controls. For 13 compounds, levels were higher in FLG mutation carriers, although differences were only statistically significant for MeP and n-PrP. Combined statistical analysis of concentrations of all the 18 compounds that were detectable in >10% of subjects, suggested that concentrations were generally higher in mutation carriers (p=0.03).
FLG loss-of-function mutation carriers have a higher internal exposure to some non-persistent chemicals, independently of atopic dermatitis. This may be due to increased trans-epidermal absorption and/or higher exposure, and mutation carriers may constitute a group susceptible to increased absorption of chemicals and topical medication.
丝聚蛋白是一种表皮蛋白，对正常的皮肤屏障功能很重要。高达 10%的欧洲人和亚洲人携带丝聚蛋白基因（FLG）功能丧失突变，这些突变似乎促进了某些化学物质的跨表皮渗透。我们之前的研究表明，与对照组相比，突变携带者对某些邻苯二甲酸酯的体内暴露更高，并且假设他们可能对其他化学物质具有更高的跨表皮渗透能力。
我们研究了具有和不具有 FLG 突变的年轻丹麦男性对非持久性化学物质的暴露情况。
从 65 名 FLG 功能丧失突变携带者和 130 名非携带者（对照组）的尿液中分析了 8 种简单酚类、6 种对羟基苯甲酸酯和 9 种紫外线滤光剂的浓度。回归分析，控制尿液稀释和混杂因素，以估计 FLG 突变状态与尿液中化学物质浓度之间的关系。
FLG 突变携带者的尿液中甲基对羟基苯甲酸酯（MeP）浓度高出 80%（13-180%），正丙基对羟基苯甲酸酯（n-PrP）浓度高出 91%（13-219%）。对于 13 种化合物，FLG 突变携带者的浓度更高，尽管只有 MeP 和 n-PrP 的浓度差异具有统计学意义。对所有 18 种可在>10%的受试者中检测到的化合物的浓度进行综合统计分析表明，突变携带者的浓度普遍较高（p=0.03）。
FLG 功能丧失突变携带者对某些非持久性化学物质的体内暴露较高，与特应性皮炎无关。这可能是由于跨表皮吸收增加和/或暴露增加所致，突变携带者可能构成对化学物质和局部用药吸收增加敏感的群体。
