F. Gloria-Bottini

Both Maternal and Foetal Genetic Factors Contribute to Macrosomia of Diabetic Pregnancy

The study of 230 diabetic mothers along with their newborn babies has shown that foetal macrosomia is associated with two specific genomic sites: phosphoglucomutase locus 1 (PGM1)-Rhesus blood group (Rh) linkage group (chromosome 1) and HindIII restriction fragment length polymorphism (RFLP) linked to insulin-like growth factor 1 (IGF1) (chromosome 12). In PGM(1)2-1 mothers carrying the E allele, there is a proportion of 8.7% of macrosomic newborns as compared with 39.6% in mothers with other genotypes. The relationship between the maternal PGM1-RhE genotype and neonatal macrosomia does not depend on the type of diabetes. The proportion of macrosomic infants is much lower among newborns carrying the IGF1HS allele of the HindIII RFLP linked to IGF1 (20%) than among IGF1F/IGF1HF newborns (55%).

Phosphotyrosine protein phosphatase and diabetic pregnancy: an association between low molecular weight acid phosphatase and degree of glycemic control

Low molecular weight acid phosphatase encoded by the highly polymorphic locus ACP 1 is a member of the protein-tyrosin phosphatase family (PTPases) which plays an essential role in the control of receptor signalling through phosphotyrosine pathways. Recent experiments have shown that purified rat liver ACP, corresponding to human ACP1, is able to hydrolyze a phosphotyrosine-containing synthetic peptide corresponding to the 1146–1158 sequence of the human insulin receptor, and shows a high affinity for it. This prompted us to analyze the degree of glycemic control in relation to ACP1 genetic variability in a sample of 214 diabetic pregnant women including IDDM, NIDDM and gestational diabetes. The ACP1 genotype was also determined in 482 non-diabetic pregnant women. In diabetic women glycemic levels in thelast trimester of pregnancy appear to be significantly associated with the ACP1 genotype, and correlated positively with ACP1 enzymatic activity. The data suggest that quantitative variations of ACP1 may influence the clincal mainifestations of diabetic disorders, and call for further studies on the role of this enzyme in the modulation of insulin-receptor phosphotyrosine pathways.

A possible genetic component of obesity in childhood. Observations on acid phosphatase polymorphism

Phenotypes of acid phosphatase with low enzymatic activity (ACP1 A and BA) are correlated with the highest degree of body mass increase observed in a sample of obese children. Since acid phosphatase probably functions as a flavin-mononucleotide phosphatase, differential modulation of flavo-enzyme activity and energy metabolism due to acid phosphatase genetic variability may explain the observed association.

Interaction at clinical level between erythrocyte acid phosphatase and adenosine deaminase genetic polymorphisms

SummaryThe effects of ACP1 phenotype on birth weight, neonatal jaundice, and obesity in children are dependent on ADA genotype. These phenomena may represent a clinical counterpart of the in vitro biochemical interactions between the two systems recently observed by our group.

Evidence of selective interaction between adenosine deaminase and acid phosphatase polymorphisms in fetuses carried by diabetic women

SummaryPossible selective interaction between genetic polymorphisms of acid phosphatase locus 1 (ACP1) and adenosine deaminase (ADA) has been investigated in a sample of 211 infants from diabetic women, and in 350 consecutive infants from normal women. Newborns from diabetic pregnancies carrying the ADA2 allele show a lower proportion of BA and CB phenotypes (heterozygotes for the main allele of ACP1 system), compared with both their mothers and normal infants. The observation suggests that, in a diabetic environment, intrauterine selection may act against double heterozygotes for the ACP1 and ADA systems.

Is there a relationship between sex of cystic fibrosis carriers and sex ratio of their offspring

SummaryData on the offspring of 198 aunts and 179 uncles of 100 cystic fibrosis index cases were analyzed. Aunts showed higher average number of liveborn sons than uncles. No significant difference was observed in the number of liveborn female offspring. When the sample was subdivided with respect to family size, the proportion of liveborn sons of aunts appeared higher than that of uncles in all classes.The present observations suggest that a female carrier may have a higher probability of male offspring than a male carrier and that she may be mainly responsible for the sex ratio deviations previously reported in sibships of cystic fibrosis patients.

Sex Ratio in Man: an Analysis of the Relationships with ABO Blood Groups and Placental Alkaline Phosphatase Phenotype

Secondary sex ratio (SR) in man is influenced by various genetic and environmental factors. It has been observed that SR in subjects of blood group B compatible with their mothers is higher than in other subjects. The analysis of 676 newborns of the Rome population and 1,684 newborns of the New Haven (Connecticut) population have confirmed a higher SR in B group subjects compatible with their mothers. The data also indicate that placental alkaline phosphatase is another genetic factor influencing SR in man and that there is a strong interaction among ABO phenotype, fetomaternal ABO compatible status and PAP phenotype concerning their effects on SR.

Rare phenotypes of placental alkaline phosphatase an analysis of relationships with some neonatal and maternal variables

SummaryPlacental alkaline phosphatase (Pl) polymorphism is due to the occurrence of three common alleles and more than fifteen rare ones at an autosomal locus. The high number and frequency (about 2%) of rare Pl alleles represent a very special case among polymorphic enzymes. Since the Pl gene is also special in that it is active only during intrauterine life, the allelic diversity and its maintenance may be connected with intrauterine environment and with fetal development.This study embraced 502 consecutive newborn infants from the white population of European descent of New Haven (Connecticut). Analysis of the relationship between rare Pl phenotypes and the following variables was carried out: gestational length, birth weight, maternal age, birth order, sex, fetal and maternal AB0 and Rh phenotypes, feto-maternal AB0 and Rh compatibility status, and previous spontaneous abortions.The results indicate a negative association of Pl rate types with the 0 phenotype in the mother and with male sex of the infant.The present data suggest that interactions with sex and with the AB0 system during intrauterine life may contribute to the maintenance of allelic, diversity in Pl system.

Haptoglobin development in newborn infants from diabetic mothers.

Haptoglobin (Hp) development during the neonatal period has been studied in 325 newborn infants from normal pregnancies and in 242 infants from diabetic mothers. In infants from diabetic mothers Hp development is delayed as compared to infants from normal pregnancies. This delay is associated with a change in the pattern of relationship between Hp development and the polymorphism of acid phosphatase (ACP1) (an enzyme which shows phosphotyrosine phosphatase (PTPase) activity). In infants from normal pregnancies who show ACP1 phenotypes with the highest activity, the appearance of Hp is accelerated as compared to other infants. In contrast, infants from diabetic pregnancies who have ACP1 phenotypes with the highest activity, show delayed Hp development.

Role of genetic variability in neonatal jaundice. A prospective study on full-term, blood group-compatible infants

A series of genetic, developmental and environmental variables have been analyzed in a prospective sample of full-term newborn babies, compatible with their mothers in the major blood group systems, in order to attempt an evaluation of the effect of these variables on serum bilirubin level during the first few days of life. Three genetic factors (PGM1, ACP1 and ADA) and three non-genetic variables (rise of bilirubin level during the first day of life, a mother with a history of previous abortion, and use of alcoholic beverages by the mother) have a significant predictive value for the separation of newborns with clinically relevant jaundice from other infants.