Preterm premature rupture of the membranes is defined as rupture of membranes before 37 weeks of gestation, which occurs in approximately 3% of all pregnancies and accounts for about one-third of spontaneous preterm births (ACOG Practice Bulletin, 1998). ... Preterm premature rupture of the membranes is defined as rupture of membranes before 37 weeks of gestation, which occurs in approximately 3% of all pregnancies and accounts for about one-third of spontaneous preterm births (ACOG Practice Bulletin, 1998). Srinivas and Macones (2005) reviewed the pathophysiology of PPROM and noted that familial clustering and ethnic differences in the incidence of PPROM suggest possible genetic influences.
Fujimoto et al. (2002) analyzed G-1607GG promoter polymorphism in the MMP1 gene (120353.0001; dbSNP rs1799750) in 75 African American infants who were born after preterm premature rupture of the membranes (PPROM) and 235 controls, and found a significant ... Fujimoto et al. (2002) analyzed G-1607GG promoter polymorphism in the MMP1 gene (120353.0001; dbSNP rs1799750) in 75 African American infants who were born after preterm premature rupture of the membranes (PPROM) and 235 controls, and found a significant association between fetal carriage of a 2G allele and PPROM (OR = 2.29; p = 0.028). In a case-control study of African American neonates and 3 SNPs in the MMP8 gene (120355.0001), Wang et al. (2004) found a statistically significant association between the 3-minor-allele haplotype, which displayed the highest MMP8 promoter activity in trophoblast cells, and preterm premature rupture of the membranes, with an odds ratio (OR) of 4.63 (p less than 0.0001). Homozygosity for the major allele promoter haplotype appeared to be protective (OR = 0.52, p less than 0.0002). In 2 case-control studies of African American neonates from pregnancies complicated by PPROM and a -656C-T SNP in the promoter of the SERPINH1 gene (600943.0001), Wang et al. (2006) found a significant association between the -656T allele and PPROM (p less than 0.0000045 for the combined studies). Wang et al. (2006) noted that SERPINH1 is located on chromosome 11q22.2 at approximately 27 Mb from the MMP8 gene, which has also been associated with PPROM, but stated that they found no evidence for linkage disequilibrium between the -656C-T SERPINH1 SNP and the previously studied MMP8 alleles. Wang et al. (2008) identified an MMP1 promoter SNP, 3447T-C (numbering based on AF007878.1; dbSNP rs2075847) and observed that the minor C allele was always methylated in vivo; functional studies demonstrated reduced promoter activity of the C allele. In a case-control study involving 284 African American neonates from pregnancies complicated by PPROM and 361 African American neonates from normal term pregnancies, Wang et al. (2008) found the minor C allele to be protective against PPROM (OR = 0.7451; p = 0.0326), consistent with its reduced promoter function. Neonates homozygous for the major T allele had 3.51-higher risk for PPROM compared to CC homozygotes (p = 0.007). Wang et al. (2008) concluded that in addition to genetic variation, DNA methylation plays a role in controlling MMP1 expression and risk of PPROM.