EFFECT OF P53 ALLELES ON PLACENTAL WEIGHT

The relationship between three p53 polymorphisms (BstUI and MspI RFLPs in exon 4 and intron 6, respectively, and a 16-bp duplication in intr on 3) in placental tissue and placental weight was examined in an atte mpt to elucidate the effect of p53 alleles on non-malignant growth. Pl acental tissue is expressing the fetal genotype. Using the quantitativ e trait loci approach, allelic frequencies of the three p53 polymorphi sms and ten alleles at other loci (AB0, FLAP, GC and ACP1) were compar ed for the high (greater than or equal to 700 g) and low (<400 g) tail s (+/-1.4 SD) of the placental weight distribution in a Swedish sample of newborns. Significant associations were found in the three p53 pol ymorphisms examined but not for the other loci, suggesting that non-ma lignant cell growth may be influenced by polymorphic p53 variants. Hig h placental weight was associated with increased frequencies of the 16 -bp duplication (A2 allele), the codon 72 BstUI Al (pro) allele and th e MspI A1 allele. These three alleles were in strong linkage disequili bria, 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 di rect functional involvement of the codon 72 pro/arg substitution in no rmal cell growth cannot be excluded.