Search

Objective Recently our group has found that the correlation between birth weight and placental weight – an index of a balanced feto-placental unit development – is influenced by genetic factors. Since adenylate kinase locus 1 (AK 1 ) is a polymorphic enzyme that plays an important role in the synthesis of nucleotides required for many metabolic functions, we have investigated the possible role of its genetic variability in the correlation between birth weight and placental weight. Study design 342 consecutive healthy newborn infants from the population of Rome (Italy) and 286 puerperae from another population from Central Italy were studied. Results The correlation coefficient between birth weight and placental weight is much higher in infants with low activity AK 1 2-1 phenotype than in those with high activity AK 1 1 phenotype. The difference between AK 1 and AK 1 2-1 is well marked only in newborns with a gestational age greater than 38 weeks and it is not influenced by sex, maternal age and maternal smoking. A similar pattern is observed with maternal AK 1 phenotype. Conclusions These results suggest that the difference in enzymatic activity between AK 1 phenotypes influencing the equilibrium among ATP, ADP, AMP and adenosine could have an important role in a balanced development of feto-placental unit.

Infection of liver cells is the first stage of malaria: parasites replicate inside the cells and then invade erythrocytes. Apoptosis mechanism in liver cells is triggered by the growth of parasites: this provides a release of parasite antigen that initiates a protective immune response. On the other hand, the parasite interferes with cell apoptosis mechanism resulting in resistance to apoptosis and successful infection [1-3]. Recently it has been observed that p53 pathway is involved in parasite survival, increased level of p53 reduces the liver parasite load whereas p53 knockout mice suffers increased liver load [4]. The p53 codon 72 is characterized by a polymorphism in exon 4 with CGC to CCC transition (rs1042522) that confers a change of arginine to proline in amino acid sequence of protein [5]. Amino acid change affects biochemical and functional properties of p53 protein. The arginine variant is a stronger apoptosis inducer while the proline variant is a stronger transcriptional activator [6]. Since apoptosis of liver cells seems to have a protective effect against malaria one would expect a positive selection of *Arg allele in areas of heavy malaria endemia. We have studied 46 consecutive newborn infants from Oristano area of Sardinia and 47 cosecutive newborn infants from area of Nuoro. Oristano was in the past a heavy malaria endemic area whereas the endemia was very light in Nuoro area. Blood was collected from the placental side of umbilical vein after cord section. Written informed consent was obtained by parents to participate to the study that was approved by I.R.B. p53 codon 72 genotypes were determined by DNA analysis as previously described [7]. Figure 1 shows the proportion of p53 codon 72 genotypes in Nuoro and Oristano areas: *Arg/*Arg genotype is much more frequent in Oristano than in Nuoro (p=0.024). The frequency of *Arg allele is 82.6% in Oristano and 69.1% in Nuoro (p=0.04). In accordance with experimental studies suggesting apoptosis of the liver cells as a defense mechanism against parasite invasion, *Arg allele favoring apoptosis seems to have been selected positively in area of Sardinia exposed in the past to heavy malaria endemia.

AIM: To investigate the role of protein tyrosin phosphatase 22 (PTPN22), maternal age at conception and sex on susceptibility and age at onset of type 1 diabetes (T1D) in Continental Italy and Sardinian populations. METHODS: Three hundred seventy six subjects admitted consecutively to the hospital for T1D and 1032 healthy subjects as controls were studied in Continental Italy and 284 subjects admitted consecutively to the hospital for T1D and 5460 healthy newborns were studied in Sardinia. PTPN22 genotype was determined by DNA analysis. Maternal age at conception and age at onset of disease were obtained from clinical records. χ2 test of independence, student t test for differences between means and odds ratio analysis were carried out by SPSS programs. Three way contingency table analysis was carried out according to Sokal and Rohlf. RESULTS: The pattern of association between PTPN22 and T1D is similar in Continental Italy and Sardinia: the proportion of *T allele carriers is 13.6% in T1D vs 6.7% in controls in Continental Italy while in Sardinia is 7.3% in T1D vs 4.4% in controls. The association between T1D and maternal age at conception is much stronger in Sardinia than in Italy: the proportion of newborn from mother aging more than 32 years is 89.3% in T1D vs 32.7% in consecutive newborn in Sardinia (P < 10-6) while in Continental Italy is 32.2% in T1D vs 19.1% in consecutive newborns (P = 0.005). This points to an important role of ethnicity. A slight prevalence of T1D males on T1D females is observed both in Continental Italy and Sardinia. PTPN22 genotype does not exert significant effect on the age at onset neither in Continental Italy nor and Sardinia. Maternal age does not influence significantly age at onset in Italy (8.2 years in T1D infants from mothers aging 32 years or less vs 7.89 years in T1D infants from mothers aging more than 32 years: P = 0.824) while in Sardinia a border line effect is observed (5.75 years in T1D infants from mothers aging 32 years or less vs 7.54 years in T1D infants from mothers aging more than 32 years: P = 0.062). No effect of sex on age at onset is observed in Continental Italy while in Sardinia female show a lower age at onset of T1D as compared to males (8.07 years in males vs 6.3 years in females: P = 0.002). CONCLUSION: The present data confirm the importance of ethnicity on susceptibility and on the age at onset of T1D.