Abstract：
Loss-of-function (LoF) mutations in the filaggrin gene (FLG) constitute the strongest genetic risk for atopic dermatitis (AD). A latitude-dependent difference in the prevalence of LoF FLG mutations was systematically evaluated. A systematic review and meta-analysis were performed to estimate the prevalence of LoF FLG mutations in AD patients and the general population by geography and ethnicity. Risk of bias was assessed by Newcastle-Ottawa Scale and Jadad score. StatsDirect, version 3 software was used to calculate all outcomes. PubMed and EMBASE were searched until 9th December 2021. Studies were included if they contained data on the prevalence of LoF FLG mutations in AD patients or from the general population or associations between AD and LoF FLG mutations and were authored in English. Overall, 248 studies and 229 310 AD patients and individuals of the general population were included in the quantitative analysis. The prevalence of LoF FLG mutations was 19.1% (95% CI, 17.3-21.0) in AD patients and 5.8% (95% CI, 5.3-6.2) in the general population. There was a significant positive association between AD and LoF FLG mutations in all latitudes in the Northern hemisphere, but not in all ethnicities. The prevalence of LoF FLG mutations became gradually more prevalent in populations residing farther north of the Equator but was negligible in Middle Easterners and absent in most African populations. FLG LoF mutations are common and tend to increase with northern latitude, suggesting potential clinical implications for future AD management. The existence of possible genetic fitness from FLG LoF mutations remains unknown.
摘要：
聚丝蛋白基因（FLG）中的功能丧失（LoF）突变构成了特应性皮炎（AD）的最强遗传风险。系统评估了LoFFLG突变患病率的纬度依赖性差异。进行了系统评价和荟萃分析，以按地理和种族评估AD患者和普通人群中LoFFLG突变的患病率。通过纽卡斯尔-渥太华量表和Jadad评分评估偏倚风险。StatsDirect,使用版本3软件计算所有结局.PubMed和EMBASE一直搜索到2021年12月9日。如果研究包含AD患者或一般人群中LoFFLG突变患病率的数据或AD与LoFFLG突变之间的关联，并且以英文撰写，则包括这些研究。总的来说,248项研究和229310例AD患者和一般人群的个体被纳入定量分析。AD患者中LoFFLG突变的患病率为19.1％（95％CI，17.3-21.0），普通人群中为5.8％（95％CI，5.3-6.2）。在北半球的所有纬度中，AD和LoFFLG突变之间存在显着正相关。但并非所有种族。LoFFLG突变的患病率在居住在赤道以北的人群中逐渐变得更加普遍，但在中东人可以忽略不计，而在大多数非洲人群中却没有。FLGLoF突变很常见，并且随着北纬的增加而增加，提示未来AD管理的潜在临床意义。来自FLGLoF突变的可能遗传适合性的存在仍然未知。
