Population-based familial aggregation of eosinophilic esophagitis suggests a genetic contribution

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:140

Article

Allen-Brady, Kristina¹  Firszt, Rafael²  Fang, John C.¹  Wong, Jathine³  Smith, Ken R.³  Peterson, Kathryn A.¹ 

[1] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA

[2] Univ Utah, Dept Pediat, Salt Lake City, UT USA

[3] Univ Utah, Huntsman Canc Inst Utah Populat Database Resource, Salt Lake City, UT USA

关键词: Eosinophilic esophagitis;    family clustering;    familiality analysis;    Utah Population Database;   

DOI  :  10.1016/j.jaci.2016.12.979

来源: Elsevier

【 摘 要 】

Background: Prior familial clustering studies have observed an increased risk of eosinophilic esophagitis (EoE) mostly among first-degree relatives, suggesting a genetic contribution to EoE, and twin studies have suggested a powerful contribution from environmental factors. Objective: This study sought to clarify the contribution of genetic factors to EoE through estimation of familial aggregation and risk of EoE in extended relatives. Methods: The Utah Population Database, a population-based genealogy resource linked to electronic medical records for health care systems across the state of Utah, was used to identify EoE cases and age, sex, and birthplace-matched controls at a 5:1 ratio. Logistic regression was used to determine the odds of EoE among relatives of EoE probands compared with the odds of EoE among relatives of controls. Results: There were 4,423 EoE cases and 24,322 controls. The population-attributable risk of EoE was 31% (95% CI, 28% to 34%), suggesting a relatively strong genetic contribution. Risks of EoE were significantly increased among first-degree relatives (odds ratio [OR], 7.19; 95% CI, 5.65-9.14), particularly first-degree relatives of EoE cases diagnosed < 18 years of age (OR, 16.3; 95% CI, 9.4-28.3); second-degree relatives (OR, 1.99; 95% CI, 1.49-2.65); and first cousins (OR, 1.35; 95% CI, 1.03-1.77), providing evidence of a genetic contribution. However, spouses of EoE probands were observed to be at increased risk of EoE (OR, 2.86; 95% CI, 1.31-6.25), suggesting either positive assortative mating or a shared environmental contribution to EoE. Conclusions: This study supports a significant genetic contribution to EoE as evidenced by increased risk of EoE in distant relatives.

【 授权许可】

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