Structure and regulation of the C1 inhibitor gene.

C1 esterase inhibitor is a M(r) approximately 105,000 glycoprotein and the sole regulation of the activities of C1r and C1s. As such, it plays an extremely important role in the regulation of the classical complement pathway. Hereditary angioedema (HAE) is the clinical manifestation of C1INH deficiency. Two types of HAE have been described. Type I HAE is characterized by low antigenic and functional levels of C1INH, while Type II HAE is characterized by normal or increased antigenic levels of C1INH with low levels of functionally active protein. C1INH is encoded by a single gene on chromosome 11. The C1INH gene consists of 8 exons and 7 introns and is approximately 1.7 x 10(4) base pairs in length. Expression of C1INH in vivo is enhanced by androgens. In vitro studies indicate that C1INH mRNA and protein levels are increased by up to 20 fold after stimulation with interferon-gamma (gamma-IFN) and to a lesser extent in response to alpha-interferon (alpha-IFN), tumor necrosis factor-alpha (TNF-alpha), Interleukin 6 (IL-6) and monocyte colony stimulating factor (M-CSF). In this chapter, we will discuss the structure of the C1INH gene and mechanisms of its regulation as well as some of the elements which may contribute to its transcriptional regulation.