Association of Filaggrin Loss of Function and Thymic Stromal Lymphopoietin Variation With Treatment Use in Pediatric Atopic Dermatitis
Association of Filaggrin Loss of Function and Thymic Stromal Lymphopoietin Variation With Treatment Use in Pediatric Atopic Dermatitis
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DOI：
10.1001/jamadermatol.2016.4467
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发表时间：
2017-03-01
期刊：
影响因子：
10.9
通讯作者：
Margolis, David J.
中科院分区：
文献类型：
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作者：
Chang, Joshua;Mitra, Nandita;Margolis, David J.
目的：确定FLG和TSLP基因型的变化是否与治疗使用的差异相对应。设计、环境和参与者：这项前瞻性队列研究招募并随访了842名儿童志愿者样本，这些儿童在儿童湿疹选择性登记处登记，为DNA提取提供唾液样本10年。入选标准包括年龄2 - 17岁，AD诊断无癌症，既往使用吡美莫司。参与者平均随访7.6年（约6396人年）；138例（16.4%）患者在10年随访中没有数据缺失。FLG和TSLP基因型的暴露评价。儿童AD是否需要在过去6个月内每隔6个月使用局部类固醇、局部钙调磷酸酶抑制剂或其他药物的自我报告结果。结果：本研究共纳入842名儿童（平均[SD]年龄1.9[2.7]岁，其中438名女孩）。比较了0、1或2个FLG功能丧失（LOF）等位基因以及TSLP rs1898671单核苷酸多态性的野生型、杂合型或纯合型患者的治疗使用情况。携带2个FLG - LOF等位基因的患者报告皮肤清除率的可能性较低（比值比[OR]， 0.20; 95% CI, 0.07-0.55），使用类固醇的可能性较高（OR, 5.04; 95% CI, 1.91-13.31）。TSLP rs1898671纯合子报告局部钙调磷酸酶抑制剂使用的可能性较小（OR, 0.16; 95% CI, 0.06-0.42），在所有停止局部钙调磷酸酶抑制剂的患者中，具有rs1898671单核苷酸多态性的患者也更有可能停止所有其他治疗（OR, 0.45; 95% CI, 0.26-0.76）。在我们的所有比较中，除了1例外，野生型和杂合型患者之间没有发现显著差异。结论和相关性治疗的使用和可能的有效性与遗传变异相关。变异仅限于具有2个FLG LOF等位基因或TSLP rs1898671纯合子的儿童，在大多数研究结果中，野生型和杂合子患者之间没有观察到显著差异。因此，在我们的分析中，关键的区分因素是FLG LOF等位基因或TSLP snp的数量，而不是这些变异的绝对存在或不存在。这可能是未来研究的一个重要考虑因素。
OBJECTIVE To determine whether variations in FLG and TSLP genotype corresponded to differences in treatment use over time.DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study recruited and followed a volunteer sample of 842 children enrolled in the Pediatric Eczema Elective Registry who provided saliva samples for DNA extraction for 10 years. Eligibility criteria included age 2 to 17 years, AD diagnosis without cancer, and prior pimecrolimus use. Participants were followed for an average of 7.6 years (approximately 6396 person-years); 138 patients (16.4%) had no missing data over 10 years of follow-up.EXPOSURES Evaluation of FLG and TSLP genotypes.MAIN OUTCOMES AND MEASURES Self-reported outcomes of whether a child's AD required the use of topical steroids, topical calcineurin inhibitors, or other medications within the past 6 months at 6-month intervals.RESULTS Overall, 842 children (mean [SD] age, 1.9 [2.7] years; 438 girls) were included in this study. Treatment use among patients with 0, 1, or 2 FLG loss of function (LOF) alleles was compared as well as those that were wildtype, heterozygous, or homozygous for the TSLP rs1898671 single-nucleotide polymorphism. Patients with 2 FLG LOF alleles were less likely to report skin clearance (odds ratio [OR], 0.20; 95% CI, 0.07-0.55) and more likely to use steroids (OR, 5.04; 95% CI, 1.91-13.31). TSLP rs1898671 homozygotes were less likely to report topical calcineurin inhibitor use (OR, 0.16; 95% CI, 0.06-0.42), and among all patients that had discontinued topical calcineurin inhibitors, those with the rs1898671 single-nucleotide polymorphism were more likely to have stopped all other treatment as well (OR, 0.45; 95% CI, 0.26-0.76). In all but 1 of our comparisons, no significant difference between wildtype and heterozygous patients were found.CONCLUSIONS AND RELEVANCE Treatment use and likely effectiveness was associated with genetic variation. Variation was limited to children with 2 FLG LOF alleles or TSLP rs1898671 homozygotes, with no significant difference observed between wildtype and heterozygous patients in the majority of the outcomes studied. Therefore, the key differentiating factor in our analyses was the number of FLG LOF alleles or TSLP SNPs rather than the absolute presence or absence of these variants. This may be an important consideration for future studies.