Significant relationship of combined ACP1/PTPN22 genotype variants with the growth of uterine leiomyomas

Objective: To analyze the interaction between ACP1 and PTPN22 concerning their effects on the growth of the tumor. In previous paper we have shown (i) that ACP1*B/*B genotype of ACP1 is negatively associated with the growth of leiomyomas and (ii) that there is a negative association of *C/*C genotype of PTPN22 with tumor growth. Materials and methods: Two hundred and three White women from the population of Rome with symptomatic leiomyomas were recruited in the University of Rome Tor Vergata. All subjects gave consent for the participation in the study that was approved by the Council of Department. ACP1 and PTPN22 genotypes were determined by DNA analysis. Results: The proportion of women with small leiomyomas decreases with the decrease of the number of protective factors and it is 37.2% in women carrying the joint genotype ACP1*B/*B-PTPN22 *C/*C (two protective factors) and 0% in women carrying no protective factors. Three way contingency table analysis by a log linear model has shown no evidence of epistatic interaction between the two genetic systems but a highly significant cooperative effect on the dimension of leiomyomas. There is a highly significant negative correlation between the number of protective factors and the dimension of leiomyomas with a minimum (cm 4.74) in women carrying the joint genotype ACP1*B/B-PTPN22 *C/*C and a maximum (cm 7.25) in women carrying no protective factors. Conclusion: The present study suggests a cooperative interaction between ACP1 and PTPN22 concerning their effects on the growth of uterine leiomyomas. The determination of the genotype of the two systems may help to evaluate the risk of clinical manifestations of this common benign tumor. Keywords: ACP1, PTPN22, Uterine leiomyoma

Association of P53 Codon 72 with Colon Cancer: the Role of Genetic Factors

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Correlation between birth weight and placental weight in healthy and diabetic puerperae

Abstract Objective The birth weight/placental weight ratio has an important predictive value for perinatal mortality and morbidity and for cardiovascular diseases in adult life. In this study, we compared the birth weight/placental weight (BW/PW) ratio and the correlation between the two parameters in diabetic women with that observed in healthy women. Materials and Methods A total of 347 consecutive newborn infants from healthy puerperae, 164 newborns from puerperae with gestational diabetes, 148 newborns from puerperae with preexisting type 1 diabetes, and 40 newborns from puerperae with preexisting type 2 diabetes have been studied from the White population of Rome. The research project was approved by the Institutional Review Board and informed written consent was obtained from the participating mothers. Results The BW/PW ratio is higher, and the correlation between the two parameters is lower in all classes of diabetes as compared to healthy puerperae. A remarkably low correlation is observed in preexisting diabetes pointing to a dissociation of fetal growth from placental growth. Discussion In diabetic pregnancy the BW/PW ratio is higher, and the correlation between birth weight and placental weight is lower in all classes of diabetic as compared to healthy puerperae pointing to a relative dissociation between the two parameters. It has been suggested that the increase of glycemic levels in diabetic pregnancy predisposes to important diseases in adult life. The dissociation of BW from PW in infants of diabetic pregnancy could be a predictor of the risk for such diseases of adult life

The genetics of feto-placental development: A study of acid phosphatase locus 1 and adenosine deaminase polymorphisms in a consecutive series of newborn infants

<p>Abstract</p> <p>Background</p> <p>Acid phosphatase locus 1 and adenosine deaminase locus 1 polymorphisms show cooperative effects on glucose metabolism and immunological functions. The recent observation of cooperation between the two systems on susceptibility to repeated spontaneous miscarriage prompted us to search for possible interactional effects between these genes and the correlation between birth weight and placental weight. Deviation from a balanced development of the feto-placental unit has been found to be associated with perinatal morbidity and mortality and with cardiovascular diseases in adulthood.</p> <p>Methods</p> <p>We examined 400 consecutive newborns from the Caucasian population of Rome. Birth weight, placental weight, and gestational length were registered. Acid phosphatase locus 1 and adenosine deaminase locus 1 phenotypes were determined by starch gel electrophoresis and correlation analysis was performed by SPSS programs. Informed verbal consent to participate in the study was obtained from the mothers.</p> <p>Results</p> <p>Highly significant differences in birth weight-placental weight correlations were observed among acid phosphatase locus 1 phenotypes (p = 0.005). The correlation between birth weight and placental weight was markedly elevated in subjects carrying acid phosphatase locus 1 phenotypes with medium-low F isoform concentration (A, CA and CB phenotypes) compared to those carrying acid phosphatase locus 1 phenotypes with medium-high F isoform concentration (BA and B phenotypes) (p = 0.002). Environmental and developmental variables were found to exert a significant effect on birth weight-placental weight correlation in subjects with medium-high F isoform concentrations, but only a marginal effect was observed in those with medium-low F isoform concentrations. The correlation between birth weight and placental weight is higher among carriers of the adenosine deaminase locus 1 allele*2, which is associated with low activity, than in homozygous adenosine deaminase locus 1 phenotype 1 carriers (p = 0.04). The two systems show a cooperative effect on the correlation between birth weight and placental weight: the highest value is observed in newborns carrying adenosine deaminase locus 1 allele*2 and acid phosphatase locus 1 phenotypes with medium-low F isoform concentration (p = 0.005).</p> <p>Conclusion</p> <p>These data suggest that zygotes with low adenosine deaminase locus 1 activity and low F activity may experience the most favourable intrauterine conditions for a balanced development of the feto-placental unit.</p

Enzyme variability and neonatal jaundice. The role of adenosine deaminase and acid phosphatase

Peer Reviewe

Further observations on associations between the ADA gene and past malaria morbidity in Sardinia

Objectives: Adenosine Deaminase (ADA) contributes to the regulation of adenosine concentration and in turn to T cell activation. Genetic variability of ADA activity may have, therefore, an important role in resistance to malaria. Indeed, previous studies in Sardinia have shown a lower frequency of ADA1*2 allele (associated with low ADA activity) in areas, where malaria was heavily endemic compared to areas where malaria was not endemic. We have now studied the ADA2 locus, another polymorphic site with two alleles ADA2 *1 and ADA2 *2 within the ADA gene. Methods: In the area of Oristano (where malaria was endemic in the past) 51 consecutive newborns and in the area of Nuoro (where malaria was not as endemic) 48 consecutive newborns were examined. ADA1 and ADA2 genotypes were determined by DNA analysis. Results: The low frequency of the ADA1*2 allele in the area where malaria was endemic is confirmed. The frequency of the ADA2*2 allele is higher in Oristano than in Nuoro resulting in a higher frequency of the ADA1*1/ADA2*2 haplotype in Oristano as compared to Nuoro. This suggests a selective advantage of this haplotype in a malarial environment. Conclusions: The ADA gene shows other polymorphic sites further studies on their role in human adaptation to malaria could be rewarding.</br

The effects of genetic and seasonal factors on reproductive success.

To search for possible effects of two polymorphisms and of the solar cycle of illumination on reproductive success

Cigarette Smoking Increases the Effect of *Arg/*Arg Genotype of P53 Codon 72 on the Susceptibility to Type 2 Diabetes in Overweight Subjects

Background: To study possible interaction between P53 codon 72 and cigarette smoking concerning their effects on the predisposition to T2D in overweight subjects.Methods: We have reexamined the data on 281 subjects admitted to the Hospital for Cardiovascular disease. The subjects gave informed consent to participate in the study that was approved by the Council of Department. P53 codon 72 genotype was determined by DNA analysis. Three way contingency table analysis was performed by a log linear model.Results: We have previously observed that *Pro/*Pro genotype of P53 codon 72 protects overweight subjects from diabetes. P53 codon 72 and cigarette smoking cooperate in the predisposition to T2D of overweight subjects. In smoking subjects carrying the *Arg/*Arg genotype the odds ratio is 15.15 vs 1.31 in carriers of *Pro allele. In non-smoking subjects the odds ratio is 6.70 in carriers of *Arg/*Arg genotype vs 2.70 in carriers of *Pro allele.Conclusions: Our observation suggests that overweight subjects with *Arg/*Arg genotype and smoking habit may have a high risk to become diabetic.</p

Smoking and human reproduction: the effect of adenylate kinase genetic polymorphism.

We investigated the possible influence of adenylate kinase genetic variability on the effect of maternal smoking on intrauterine selection and development. Adenylate kinase locus 1 belongs to a family of monophosphate kinases that plays an important role in the synthesis of nucleotides involved in several metabolic functions. Three hundred forty-five newborn consecutive infants from the Caucasian population of Rome and 360 consecutive infants from the Caucasian population of Penne were studied. The proportion of newborns carrying AK1*2 allele was analyzed in relation to smoking and maternal age. The effect of smoking on birth weight was also analyzed in relation to AK1 phenotype and maternal age. Statistical analyses have been performed according to SPSS programs. In offspring of women aged 28 years or less, the proportion of newborns carrying the AK1*2 allele is much higher in smoking than in nonsmoking mothers (13.2% versus 2.6%). Such association is lacking in mothers aged more than 28 years (6.5% versus 9.2%). The negative effects of smoke on birth weight is more marked in AK11 mothers than in AK1*2 carriers. The data suggest that zygotes carrying AK1*2 allele are relatively protected from the damaging effects of smoking, resulting in a relatively higher proportion of newborns carrying this allele among smoking mothers