A 12‐bp deletion in the 5'‐flanking region of the SERPINH1 gene affects promoter activity and protects against preterm premature rupture of membranes in African Americans

We identified a novel 12‐bp deletion NT_033927.7: g.5495364_5495375del in the 5'‐flanking region of the SERPINH1 gene that increases promoter activity. The 12‐bp deletion is in linkage disequilibrium with the minor “T” allele of the ‐656 C/T SNP (NT_033927.7(SERPINH1):g.5495402C>T) that reduces promoter activity in amnion fibroblast cells and is associated with a significantly increased risk of preterm birth as a result of premature rupture of membranes. In a case‐control study, fetal carriage of the 12‐bp deletion was found to protect against PPROM, apparently overcoming the influence of the SERPINH1 ‐656 “T” allele. These studies define a new haplotype in the SERPINH1 gene that modifies risk of an adverse obstetrical outcome. © 2007 Wiley‐Liss, Inc.