Department of Dermatology, Zealand University Hospital, Roskilde, Denmark.
Danish Twin Registry, Department of Epidemiology, Biostatistics and Biodemography, University of Southern Denmark, Odense, Denmark.
Br J Dermatol. 2022 Jan;186(1):78-85. doi: 10.1111/bjd.20654. Epub 2021 Sep 28.
Hidradenitis suppurativa (HS) is a recurrent inflammatory skin disease that, apart from rare causative loss-of-function mutations, has a widely unknown genetic aetiology.
To estimate the relative importance of genetic and environmental factors underlying susceptibility to HS.
Via the Danish Twin Registry and the Danish National Patient Registry we pulled together information on zygosity with that of HS status. Cases of HS were identified by the International Classification of Diseases (ICD)-8 (705·91) and ICD-10 (L73·2). Heritability was assessed by the classic biometric model and the possibility of gene-gene interaction via the multilocus modelling approach.
Among 100 044 registered twins, we found 170 twins (from 163 pairs) diagnosed with HS. The seven concordant pairs were all monozygotic. Monozygotic twins had a case-wise concordance rate of 28% [95% confidence interval (CI) 7-49], corresponding to a familial risk of 73 (95% CI 13-133) times that of the background population. The biometrical modelling suggested a heritability of 0·80 (95% CI 0·67-0·93), and the multilocus index estimate was 230 (95% CI 60-400). This is highly indicative of gene-gene interactions, with the possibility of up to six interacting loci.
This twin study was substantially larger and employed a more valid phenotype than previous studies. Genetics account for the majority of HS susceptibility, and HS is most likely caused by gene-gene interactions rather than monogenetic mutations or solely additive genetic factors. New approaches aimed at assessing potential interactions at a single-nucleotide polymorphism (SNP)-SNP level should be implemented in future HS genome-wide association studies.
化脓性汗腺炎（HS）是一种复发性炎症性皮肤病，除了罕见的功能丧失性突变外，其遗传病因尚不清楚。
估计遗传和环境因素在 HS 易感性中的相对重要性。
通过丹麦双胞胎登记处和丹麦国家患者登记处，我们将同卵性和 HS 状态的信息汇总在一起。HS 病例通过国际疾病分类（ICD）-8（705·91）和 ICD-10（L73·2）进行识别。通过经典的生物计量模型评估遗传率，并通过多基因模型方法评估基因-基因相互作用的可能性。
在 100044 名登记的双胞胎中，我们发现有 170 对双胞胎（来自 163 对）被诊断患有 HS。7 对一致的双胞胎均为同卵双胞胎。同卵双胞胎的病例一致性率为 28%（95%置信区间 7-49%），对应的家族风险是背景人群的 73 倍（95%置信区间 13-133 倍）。生物计量模型表明遗传率为 0.80（95%置信区间 0.67-0.93），多基因指数估计值为 230（95%置信区间 60-400）。这高度表明存在基因-基因相互作用，可能存在多达六个相互作用的基因座。
本双胞胎研究的规模明显更大，并且采用了比以往研究更有效的表型。遗传因素占 HS 易感性的大部分，HS 最有可能由基因-基因相互作用引起，而不是由单基因突变或单纯的累加遗传因素引起。在未来的 HS 全基因组关联研究中，应采用新的方法来评估单核苷酸多态性（SNP）-SNP 水平上的潜在相互作用。
