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(SERPINHI):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 SERPINHI -656 T allele. These studies define a new haplotype in the SERPINHI gene that modifies risk of an adverse obstetrical outcome. (C) 2007 Wiley-Liss, Inc.