Functional maternal catechol-O-methyltransferase polymorphism and fetal growth restriction

Objectives The pathophysiologic processes that occur at the cellular and molecular levels in intrauterine fetal growth restriction are largely unknown. Catechol-O-methyltransferase (COMT) is a phase II enzyme that inactivates catechol estrogens by transfer of a methyl group. A functional VaI158Met polymorphism in the COMT gene has been known as a susceptible marker for breast cancer. The aim of this study was to examine the association between this polymorphism and fetal growth. Methods A consecutive series of 412 women who experienced singleton deliveries was assessed in the birth cohort study. Genotyping of COMT and CYP17A1 polymorphisms was determined by allelic discrimination using fluorogenic probes and the 5'nuclease assay. Results The adjusted odds ratio for the risk of low birth weight (< 2.500 g) in women with homozygous low-activity (COMT-L) alleles was 2.98 (95% confidence interval, 1.10-8.11). The mean birth weight of infants whose mothers were homozygous for COMT-L was less than that of infants whose mothers had at least one high-activity (COMT-H) allele (2.610 versus 2.800g, P=0.07). The odds ratio for the risk of intrauterine fetal growth restriction, defined as birth weight < 10th percentile or < mean-1.5 SD, in women homozygous for COMT-L alleles was 2.63/2.57 (95% confidence interval, 1.14-6.05/0.96-6.88). In the recessive genotype model, the odds ratios for the risk of low birth weight and intrauterine fetal growth restriction in women homozygous for COMT-L were 3.36 (95% confidence interval, 1.30-8.65) and 2.89/2.65 (95% confidence interval, 1.31-6.34/1.06-6.65), respectively. A positive association exists between birth weight and the homozygous CYP17A1 A2 genotype (P < 0.01). When both COMT and CYP17A1 genotypes were considered, the highest risk of low birth weight/intrauterine fetal growth restriction was found among women with the homozygous COMT-L and CYP17A1 A1 genotype. The odds ratio for the risk of intrauterine fetal growth restriction (< 10th percentile) in those women was 5.35 (95% confidence interval, 1.15-25.0). Conclusion Our findings suggest that the allele encoding low-activity COMT may be a susceptible marker for intrauterine fetal growth restriction.