From an ACE polymorphism to genome-wide searches for eQTL

Angiotensin I-converting enzyme (ACE, or DCP1) is a zinc metallopeptidase that converts angiotensin I into the vasoactive and aldosterone-stimulating peptide angiotensin II and cleaves bradykinin into inactive peptides. Plasma ACE measurement is widely used for the diagnosis of sarcoidosis. While enzyme concentrations are highly stable in an individual, there is a high level of interindividual variability. In 1990, we identified an insertion/deletion polymorphism in ACE that functions as a quantitative trait locus (QTL), accounting for half of the interindividual variability. Since then, technological advances have allowed for the elucidation of expression QTLs (eQTL). Such studies are allowing researchers to determine how underlying genetic predisposition contributes to human disease.