Effect of p53 Alleles on Placental Weight

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Abstract
The relationship between three p53 polymorphisms (BstUI and MspI RFLPs in exon 4 and intron 6, respectively, and a 16-bp duplication in intron 3) in placental tissue and placental weight was examined in an attempt to elucidate the effect of p53 alleles on non-malignant growth. Placental tissue is expressing the fetal genotype. Using the quantitative trait loci approach, allelic frequencies of the three p53 polymorphisms and ten alleles at other loci (ABO, PLAP, GC and ACP1) were compared for the high (> or = 700 g) and low (< 400 g) tails (+/- 1.4 SD) of the placental weight distribution in a Swedish sample of newborns. Significant associations were found in the three p53 polymorphisms examined but not for the other loci, suggesting that non-malignant cell growth may be influenced by polymorphic p53 variants. High placental weight was associated with increased frequencies of the 16-bp duplication (A2 allele), the codon 72 BstUI A1 (pro) allele and the MspI A1 allele. These three alleles were in strong linkage disequilibria, and high placental weight was therefore associated with the 2-1-1 haplotype. The fact that the strongest associations were found with intronic markers suggests linkage disequilibrium with growth-promoting sites at the p53 molecule as the most likely mechanism, although a direct functional involvement of the codon 72 pro/arg substitution in normal cell growth cannot be excluded.

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