Association of insertion/deletion polymorphism of the angiotensin‐converting enzyme gene with angio‐oedema accompanying chronic urticaria but not chronic urticaria without angio‐oedema or the autologous serum skin test response

Abstract

Chronic urticaria is defined as the daily or almost daily occurrence of weals for more than 6 weeks. The underlying pathophysiology is reported to be mast cell activation, with release of mast cell mediators, predominantly histamine. Substance P is a neuropeptide and has the capacity to provoke histamine release from skin mast cells. Angiotensin-converting enzyme (ACE), widely expressed in skin, is one of the major peptidase for the degradation of substance P. An insertion/deletion polymorphism (I/D) in the ACE gene has been reported to be related to the levels of enzyme. An increase in substance P levels due to a polymorphism in ACE gene might be related to the pathology. Thus, we aimed to investigate whether there is an association between ACE I/D polymorphism and chronic ordinary urticaria. Ninety-five patients with chronic ordinary urticaria were recruited and divided into two groups according to autologous serum skin test status and accompanying angio-oedema. One hundred and sixty-one healthy subjects were enrolled as control group. All participants were genotyped for I/D polymorphism in intron 16 of the ACE gene by polymerase chain reaction. A statistically significant association was not found between ACE I/D polymorphism and chronic ordinary urticaria. Further analyses of chronic ordinary urticaria patients showed that ACE I/D polymorphism was not associated with autologous serum skin test status of patients. However, the frequencies of II genotype and I allele were statistically significantly higher in chronic ordinary urticaria patients with accompanying angio-oedema with regard to angio-oedema-negative patients (II genotype: 24% vs. 9%, P = 0.0002; I allele: 58% vs. 27%, P = 0.0001) and control group (II genotype: 24% vs. 19%, P = 0.01; I allele: 58% vs. 41%, P = 0.03). The results of this study suggest no evidence of an association between ACE I/D polymorphism and risk of developing chronic ordinary urticaria. However, it can be a contributing factor to susceptibility of angio-oedema in chronic ordinary urticaria.