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In Japan, substantial interest has recently focused on wheatdependent exercise-induced anaphylaxis (WDEIA) caused by percutaneous and/or rhino-conjunctival sensitization of hydrolyzed wheat protein (HWP), Glupearl 19S, which was used as ingredient of popular facial soap of which 46 million units had been sold. To date, more than 2000 people in Japan have been diagnosed with HWP-sensitized WDEIA (HWP-WDEIA).1e3 Apart from the sensitization pathway, patients with HWP-WDEIAmanifest variable levels of immediate-type response following natural wheat product ingestion and exercise, which is quite similar to conventional WDEIA.1e3 Although some genetic factors may be responsible for the manifestation of WDEIA, its pathomechanism remains largely unknown. WDEIA is a rare disease in our country but we have encountered some patients with near-fatal anaphylactic reactions. Therefore this mechanism and genetic factors associated with the risk for WDEIA should be investigated. It has been reported that the angiotensin-converting enzyme (ACE) genotype was associated with cardiovascular, thrombotic and metabolic disorders.4e6 Very recently, the ACE genotype was implicated in the manifestation of anaphylactic reactions to food, venom, and drugs.7 The ACE gene, located at chromosome 17q23.3, has two allelic forms, with the presence (I) or absence (D) of a 287-base-pair intron. The II and ID genotypes are significantly more common than DD in patients with anaphylaxis, with odds ratios (ORs) of 44 and 5.6, respectively.7 DD genotypes has been reported as a risk factor of coronary heart disease and an effect modifier of its therapeutic effect.4e6 In the present study, we examined the ACE genotypes of 47 HWP-WDEIA patients with a median age of 46.3 (range 16e75). The allergologic data of the patients are shown in Table 1. We isolated DNA from the patients' oral mucosa with the DNeasy Blood &Tissue Kit (Qiagen KK, Tokyo, Japan), and amplified it by PCR. Samples were genotyped using the quenching probe method for a single-nucleotide polymorphism (rs4341). Allele frequency of the cases with WDEIA followed the HardyeWeinberg equilibrium (p 1⁄4 0.88). The genotypes for WDEIA patients are shown in Table 2, along with the previously published data in a prospective population-based cohort study for 2125 subjects aged 40 or older Japanese living in the town of Hisayama, a suburban community in Fukuoka prefecture, and participating in periodic health check-

Angiotensin-converting enzyme genotype is a risk factor for wheat-dependent exercise-induced anaphylaxis sensitized with hydrolyzed wheat protein