Association of the polymorphism 12109g>A from the REN gene as a risk factor for preterm birth

Abstract

Introduction: Preterm birth is the most important cause of neonatal mortality and morbidity. It is a multifactorial disease with different etiologies, including genetic factors. Genetic variability is represented by single nucleotide polymorphisms (SNPs) in genes of proteins involved in the contractile activity. We determine the association between SNP 12109G> A in REN associated with preterm birth and premature rupture of membrane.

Materials and methods: A study of cases ( N=112, 22-36 weeks of gestation; mean: 31, 95% confidence interval 30.7-32.2) and controls ( N=66; 38-40 weeks of gestation from the last menstrual period; mean: 39.8, 95% confidence interval 38.9-39.4) was performed. Genomic DNA was isolated in all patients from peripheral blood. The SNP 12109G> A ( Mbo I) in REN was typified by PCR-restriction fragment length polymorphism.

Results: A significant difference in the case group for the SNP 12109G>A was observed. The A allele was increased in women with preterm birth (81% cases vs. 15% control, p<0.0000004). There was also a significant difference between genotypes, mainly an excess of G/A heterozygotes in women with preterm birth (60% cases vs. 23% controls). The phenotype 12109G> A has odds ratio 6.62 (95% confidence interval 3.14-14.15), which means a high risk of preterm birth/premature rupture of membrane in presence of allele A, both in homozygotes and in heterozygotes.

Conclusion: Allelic frequency of A of SNP 12109G>A was higher in women with preterm birth than in women with normal vaginal delivery and could be considered a risk factor.

Keywords: Mbo I; PCR-RFLP; Preterm birth; REN gene; SNPs.

Figure 1.

Characterization of polyacrylamide gel for SNP 12109G> A (Mbo I) by PCR restriction fragment length SNP. Lines are numbered from left to right. Homozygous G/G (Lanes 2, 3, 8, 11, 12, 17 and 20), homozygous A/A (lanes 4, 7, 13 and 14) and heterozygous G/A (Lanes 1, 5, 6, 15, 18 and 19) are observed. Molecular weight marker 50 bp (Lane 10).