Supplementary Material for: Atopic Dermatitis in Urban Indonesian Children: A Case-Control Study of the Prevalence of Filaggrin Loss-of-Function Variants and Sociodemographic Factors at a Tertiary Referral Hospital

Introduction: Research on atopic dermatitis (AD) in children has predominantly focused on European and Western populations. Although there is evidence suggesting a connection between sociodemographic and cultural factors and AD, studies involving Asian populations are notably limited. This study profiled filaggrin (FLG) loss-of-function (LOF) variants, estimates their prevalence, and investigates the association between sociodemographic and cultural factors with AD among children in Indonesia as one of the most densely populated developing countries in Asia.

Methods: A case control study was conducted at the Pediatric Dermatology Clinic of Dr. Hasan Sadikin General Hospital in Bandung, the capital city of West Java, Indonesia. Children were included from April to December 2022. AD was diagnosed using Hanifin and Rajka criteria. Controls were children without AD of similar age and sex. Sociodemographic data were collected. We sequenced the coding region of FLG using single-molecule molecular inversion probes and next-generation sequencing. Descriptive statistics were used to summarize demographic characteristics. Univariate and multivariate analysis estimated adjusted odds ratios (aOR) and 95% confidence intervals.

Results: We enrolled 218 participants. FLG LOF variants were 3.6% in AD and 1.9% in controls; detected variants included c.7487del, c.2282_2285del, and c.1501C>T. Parental history of atopy is significantly associated with children developing AD, with aOR of 6.59 (95% CI: 3.18-13.63) for mothers and aOR 3.86 (95% CI: 1.73-8.62) for fathers. After adjustment, sociodemographic and cultural variables were not statistically significant in multivariate models.

Conclusion: In Indonesian children, FLG LOF variants were infrequent, contrasting with European cohorts. Parental atopy remained a strong determinant, and no independent associations with sociodemographic or cultural factors were detected.

引言：目前针对儿童特应性皮炎（atopic dermatitis, AD）的研究主要聚焦于欧洲及西方人群。尽管已有证据表明社会人口学与文化因素和特应性皮炎存在关联，但针对亚洲人群的相关研究仍显著不足。本研究以亚洲人口最稠密的发展中国家之一印度尼西亚为研究场景，对儿童丝聚蛋白（filaggrin, FLG）功能丧失（loss-of-function, LOF）变异进行分型，估算其流行率，并探究社会人口学与文化因素和该国儿童特应性皮炎之间的关联。
方法：本研究为病例对照研究，于印度尼西亚西爪哇省首府万隆的哈山·萨迪金博士总医院儿科皮肤科门诊开展，研究对象纳入时间为2022年4月至12月。采用韩-拉标准（Hanifin and Rajka criteria）诊断特应性皮炎，以年龄、性别匹配的非特应性皮炎儿童作为对照。收集研究对象的社会人口学资料，采用单分子分子倒置探针（single-molecule molecular inversion probes）联合下一代测序（next-generation sequencing）技术对丝聚蛋白的编码区进行测序。采用描述性统计总结人口学特征，通过单变量及多变量分析估算校正比值比（adjusted odds ratios, aOR）与95%置信区间。
结果：本研究共纳入218名研究对象。特应性皮炎组丝聚蛋白功能丧失变异的检出率为3.6%，对照组为1.9%；检出的变异包括c.7487del、c.2282_2285del及c.1501C>T。父母特应性病史与儿童罹患特应性皮炎显著相关：母亲特应性病史的校正比值比为6.59（95%CI：3.18~13.63），父亲特应性病史的校正比值比为3.86（95%CI：1.73~8.62）。经校正后，多变量模型中社会人口学与文化因素变量均无统计学显著性。
结论：在印度尼西亚儿童群体中，丝聚蛋白功能丧失变异的检出率较低，这与欧洲队列的研究结果形成对比。父母特应性病史仍是儿童特应性皮炎的强危险因素，未发现社会人口学或文化因素与特应性皮炎存在独立关联。