No relation between angiotensin-converting enzyme gene polymorphism and dermal response to bradykinin in healthy subjects.
1. The dermal wheal response to bradykinin is increased by drugs which inhibit angiotensin-converting enzyme, and thus provides a measure of angiotensin-converting enzyme activity at the tissue level. An insertion/deletion polymorphism of the angiotensin-converting enzyme gene predicts serum angiotensin-converting enzyme activity, but its relation to angiotensin-converting enzyme activity in tissue is unclear. 2. The relations between angiotensin-converting enzyme genotype and wheal responses to intradermal bradykinin were studied in 105 healthy subjects: 30 of genotype DD, 51 of genotype ID and 24 of genotype II. Dermal wheal area was measured by digitized planimetry and the angiotensin-converting enzyme genotype by polymerase chain reaction. 3. Bradykinin produced significant linear log dose-wheal area responses. The potency of bradykinin by parallel line bioassay did not differ significantly between the genotypes; the potency in the II subjects relative to DD subjects was 1.25 (95% confidence interval: 0.83-1.88). 4. Although the angiotensin-converting enzyme gene polymorphism is a consistent and powerful predictor of serum angiotensin-converting enzyme activity, it does not appear to predict tissue angiotensin-converting enzyme activity as measured by dermal responses to bradykinin.
Chadwick
I G
IG
University Department of Medicine and Pharmacology, Royal Hallamshire Hospital Sheffield, U.K.
Kraskiewicz
M
M
Yeo
W W
WW
Higgins
K S
KS
Jackson
P R
PR
Ramsay
L E
LE
D000328:Adult; D001920:Bradykinin / Q000494:pharmacology; D003877:Dermatitis, Contact / Q000201:enzymology* / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism
D006632:Histamine; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin