■额叶纤维性脱发(FFA)是一种越来越普遍的毛囊性扁平苔藓,导致不可逆的脱发,主要在绝经后的个体。女性FFA的早期全基因组荟萃分析确定了与自身抗原呈递和T细胞稳态有关的基因中的风险位点,包括HLA-B*07:02、ST3GAL1和SEMA4B。然而,CYP1B1,对激素代谢很重要,还涉及丝氨酸在453位取代天冬酰胺(c.1358A>G,p.Asn453Ser)表现出对FFA的保护作用。增加对遗传和环境变量及其相互作用的理解将提高对疾病发病机理的理解,并有可能为风险缓解策略提供信息。
■为了调查口服避孕药(OCP)的使用是否调节CYP1B1中常见错义变体的保护作用(c.1358A>G,p.Asn453Ser)关于FFA风险。
■这项使用病例对照设计的基因-环境相互作用研究招募了来自英国皮肤科诊所的女性FFA患者。患者与来自英国生物银行的无关年龄和血统匹配的女性对照个体以1:66的比例进行匹配,由全基因组基因型的前4个主成分确定。数据收集时间为2015年7月至2017年9月,分析时间为2022年10月至2023年12月。
■主要结果是使用OCP对CYP1B1错义变异体对女性FFA风险的贡献的调节作用,以及通过具有乘法相互作用项的逻辑回归模型评估的正式基因-环境相互作用检验,在加性遗传模型相互作用项的假设下,在加性遗传模型的假设下。
■在489名女性FFA患者中,平均(SD)年龄为65.8(9.7)岁,370人(75.7%)有OCP使用史。在34254名年龄和血统匹配的对照个体中,平均(SD)年龄为65.0(8.4)岁,以前使用OCP的报告为31177例(91.0%)。在报告使用OCP的个体中观察到女性FFA与CYP1B1风险等位基因之间的关联(优势比,1.90[95%CI,1.50-2.40];P=8.41×10-8),但在那些没有记录暴露于OCP的人群中没有(赔率比,1.16[95%CI,0.82-1.64];P=.39)。完整的基因-环境相互作用模型证明了c.1358A之间的显着加性统计相互作用,p.453Asn,以及OCP对FFA风险的使用历史(或相互作用,1.63[95%CI,1.07-2.46];P=.02)。
■这种基因-环境相互作用分析表明,CYP1B1错义变体对FFA风险的保护作用可能是由暴露于OCP介导的。仅在有OCP病史的参与者中,在CYP1B1的453位编码天冬酰胺的等位基因与FFA的几率增加相关。
UNASSIGNED: Frontal fibrosing alopecia (FFA) is an increasingly prevalent form of follicular lichen planus, causing irreversible hair loss predominantly in postmenopausal individuals. An earlier genome-wide meta-analysis of female FFA identified risk loci in genes implicated in self-antigen presentation and T-cell homeostasis, including HLA-B*07:02, ST3GAL1, and SEMA4B. However, CYP1B1, which is important for hormone metabolism, was also implicated with the substitution of serine for asparagine at position 453 (c.1358A>G, p.Asn453Ser) exhibiting a protective effect against FFA. Increasing understanding of genetic and environmental variables and their interactions will improve understanding of disease pathogenesis and has the potential to inform risk mitigation strategies.
UNASSIGNED: To investigate whether oral contraceptive pill (OCP) use modulates the protective effect of the common missense variant in CYP1B1 (c.1358A>G, p.Asn453Ser) on FFA risk.
UNASSIGNED: This gene-environment interaction study using a case-control design enrolled female patients with FFA from UK-based dermatology clinics. The patients were matched with unrelated age- and ancestry-matched female control individuals derived from UK Biobank in a 1:66 ratio, determined by the first 4 principal components from genome-wide genotypes. Data were collected from July 2015 to September 2017, and analyzed from October 2022 to December 2023.
UNASSIGNED: The main outcomes were the modulatory effect of OCP use on the contribution of the CYP1B1 missense variant to female FFA risk and a formal gene-environment interaction test evaluated by a logistic regression model with a multiplicative interaction term, under the assumptions of an additive genetic model interaction term, under the assumptions of an additive genetic model.
UNASSIGNED: Of the 489 female patients with FFA, the mean (SD) age was 65.8 (9.7) years, and 370 (75.7%) had a history of OCP use. Of the 34 254 age- and ancestry-matched control individuals, the mean (SD) age was 65.0 (8.4) years, and previous OCP use was reported in 31 177 (91.0%). An association between female FFA and the CYP1B1 risk allele was observed in individuals who reported OCP use (odds ratio, 1.90 [95% CI, 1.50-2.40]; P = 8.41 × 10-8) but not in those with no documented exposure to OCPs (odds ratio, 1.16 [95% CI, 0.82-1.64]; P = .39). A full gene-environment interaction model demonstrated a significant additive statistical interaction between c.1358A, p.453Asn, and history of OCP use on FFA risk (OR for interaction, 1.63 [95% CI, 1.07-2.46]; P = .02).
UNASSIGNED: This gene-environment interaction analysis suggests that the protective effect of the CYP1B1 missense variant on FFA risk might be mediated by exposure to OCPs. The allele that encodes an asparagine at position 453 of CYP1B1 was associated with increased odds of FFA only in participants with OCP history.