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N Bottini

Publications and source records attributed to N Bottini.

At least 37 records · Page 2Linked to original sources
PubMed2002

Smoking and the genetics of signal transduction: an association study on retinopathy in type 1 diabetes.

BACKGROUND: Recent studies suggest a complex association between smoking and retinopathy that probably depends on the interaction between many variables. We have reported an association between ACP1 phenotype and retinopathy in type 1 diabetes. Additionally, the deleterious effects of smoking on intrauterine growth are dependent on ACP1, a low-molecular-weight tyrosine phosphatase that modifies signal transduction. We examine here the interaction between smoking and ACP1 as a mediator of susceptibility to diabetic retinopathy in a sample of puerperae with type 1 diabetes. SUBJECTS AND METHODS: Seventy-eight women who had just delivered live infants were studied. ACP1 phenotype was determined by starch gel electrophoresis. Three-way contingency tables were analyzed. RESULTS: There is a significant epistatic interaction between smoking and ACP1 phenotype concerning their effects on retinopathy. In subjects with low ACP1 activity, frequency of retinopathy was slightly higher in smokers than in nonsmokers. However, in subjects with medium-high ACP1 activity, frequency of retinopathy was significantly lower in smokers than in nonsmokers. A logistic regression analysis using retinopathy as the dependent variable revealed that smoking, ACP1, and ACP1 by smoking interaction, as well as the interaction between smoking and age of the women, are the most robust predictors of retinopathy. CONCLUSIONS: The effect of smoking on retinopathy in women with type 1 diabetes depends on many variables, which supports the hypothesis of complex interactions between smoking and other variables in the pathogenesis of this disease. Variability of genetic factors involved in signal transduction may affect endothelium proliferation through the regulation of growth factors and through regulation of glycemic levels. Because cigarette smoke influences signal transduction, its impact on diabetic retinopathy may be mediated by ACP1.

Adult↗
PubMed2001

Autism: evidence of association with adenosine deaminase genetic polymorphism.

Reduced adenosine deaminase (ADA) activity has been reported in sera of autistic children relative to controls. Additionally, the Asn allele of the ADA Asp8Asn polymorphism has been associated with reduced enzymatic activity. Therefore, we studied this polymorphism in autistic children and controls from two Italian populations. We observed a significantly elevated frequency of the low-activity Asn allele in the total sample of autistic cases relative to controls (P < 0.00001), and in both study populations (P < 0.001 and P < 0.025). We suggest that this putative genotype-dependent reduction in ADA activity may be a risk factor for the development of autism.

Adenosine Deaminase↗
PubMed2001

ABO/Secretor genetic complex and susceptibility to asthma in childhood.

A positive association has recently been reported in adult subjects between O/nonSecretor phenotype and asthma. To confirm this association, this study investigated the joint ABO/Secretor phenotype in a cohort of 165 asthmatic children. Three-hundred and sixty-two consecutive newborn infants from the same population were also studied as controls. The proportion of O/nonSecretor in asthmatic children was higher than in controls, thus confirming the association found in adults. The association was more marked in males than in females. In males, the pattern of association between the joint ABO/Secretor phenotype and asthma is dependent on the age at on-set of symptoms. Since the oligosaccharide composition of cell membrane and mucosal secretions is controlled by the cooperative interaction of ABO and Secretor genes, and since such composition influences the adhesion of infectious agents, the age pattern could reflect a more general interaction between developmental maturation and oligosaccharide structure concerning their effects on susceptibility to viral and bacterial agents.

ABO Blood-Group System↗
PubMed2001

Maternal-fetal interaction in the ABO system: a comparative analysis of healthy mothers and couples with recurrent spontaneous abortion suggests a protective effect of B incompatibility.

We investigated the possible differential effects of A and B blood group materno-fetal incompatibility on human fertility through a comparative analysis of couples with recurrent spontaneous abortion (RSA) and healthy mothers. ABO phenotype was determined in 5180 healthy mothers and their newborn babies from the population of Sassari (Sardinia) and in 1359 healthy puerperae (women who have just given birth) from the population of Rome. Mother-newborn joint ABO distribution in healthy mothers was compared with wife-husband joint ABO distribution in RSA couples. Distortions from expected distribution were evaluated by symmetry analysis. In both RSA couples and healthy mothers significant deviation from expected symmetry patterns were observed. Deviations in RSA are in the opposite direction to those observed in healthy puerperae. The most important difference observed concerned the symmetric joint phenotypes mother (women) A/infant (husband) B (B incompatible) and mother (women) B/infant (husband) A (A incompatible). A low number of B incompatible in RSA couples and a high number of B incompatible in healthy mothers was observed. The phenomenon is much more evident in women aged 24-28 years, a period of maximum fecundity. It is possible that the presence of anti-B immunoglobulin in the mother might have a protective effect against fetal loss in some cases of mother-infant ABO incompatibility.

ABO Blood-Group System↗
PubMed2001

The genetics of signal transduction and the outcome of diagnostic tests in growth retardation.

The effects of 'normal' genetic variability of signal transduction on endocrine function may be more evident during stimulation tests than is observed in basal states, thereby contributing to a greater understanding of the possible role of signal transduction genetics in the pathogenesis of endocrine disorders. In the present study, we have studied the outcome of growth hormone (GH) stimulation testing by insulin in growth-retarded children in relation to the genotype of ACP1 (acid phosphatase locus 1; also referred to as cLMWPTP, cytosolic low molecular weight phosphotyrosine phosphatase). ACP1 is an enzyme, expressed as two distinct isoforms designated F and S, that down-regulates insulin receptor signal transduction and which shows a genetic polymorphism with strong quantitative enzymatic differences among genotypes. In this study, we examined 116 growth-retarded children of which 101 were genotyped for ACP1. We found that the basal level of GH is higher in ACP1 genotypes with low concentrations of the S isoform than in genotypes with high S isoform concentrations (P<0.02). Additionally, during GH stimulation with insulin, the genotypes with low S isoform concentrations were found to perform better (P<0.005) and to react more promptly than the genotypes with high S isoform concentrations (P<0.05). These findings suggest that high S isoform ACP1 activity slows down the effect of insulin, resulting in a retardation of its metabolic effect.

Acid Phosphatase↗
PubMed2000

Inflammatory bowel disease: Are there gender differences in the genetics of signal transduction? A preliminary study of cytosolic low molecular weight protein tyrosine phosphatase.

The phenotype of cytosolic Low Molecular Weight Protein Tyrosine Phosphatase (cLMWPTP or ACP1), an enzyme involved in signal transduction of insulin, PDGF and T-cell receptors, has been determined in 71 patients with Crohn's Disease (CD: 37 males and 34 females), 49 patients with Ulcerative Colitis (UC: 27 males and 22 females) and 358 consecutive newborns (194 males and 164 females). cLMWPTP phenotypes showing a high concentration of F isoforms are associated with CD in females and with UC in males. Since PTPases counteract the effects of protein tyrosines kinases, a high concentration of F isoform of cLMWPTP may influence the mucosal response to pathogenic factors, increasing susceptibility to CD in females and to UC in males.

Colitis, Ulcerative↗
PubMed2000

RH blood groups and diabetic disorders: is there an effect on glycosylated hemoglobin level?

Recent cloning of RH genes has elucidated their structure, suggesting that RH proteins are part of an oligomeric complex with transport function in the erythrocyte. This observation prompted us to investigate a possible relationship between the RH system and the glycosylated hemoglobin level (Hb A(1c)) in diabetes. This compound is considered an important indicator- of glycemic control in diabetic disorders. We studied 278 subjects with non-insulin-dependent diabetes mellitus (NIDDM) from the population of Penne, Italy. Glycemic and glycosylated hemoglobin (Hb A(1c)) levels are associated with RH phenotype. Glucose and Hb A(1c) levels are increased in DCcEe subjects and decreased in ddccee subjects as compared to the mean values for other genotypes. Sex, age at onset of disease, duration of disease, and age of patients were also considered. Correlation analysis suggests that these variables influence glycemia directly and Hb A(1c) indirectly. The RH system, on the other hand, seems to influence the Hb A(1c) level directly. Preliminary data on 53 children with insulin-dependent diabetes mellitus (IDDM) from Sardinia seem to confirm the relationship between RH and Hb A(1c) observed in NIDDM. Since glycosylated hemoglobin is found inside red blood cells, the relationship between RH genetic variability and Hb A(1c) level suggests that RH proteins may influence glucose transport through red cell membrane and/or hemoglobin glycation.

Adult↗
PubMed1999

Haptoglobin genotype and natural fertility in humans.

OBJECTIVE: To study the possible relation between human natural fertility and haptoglobin (Hp) genotype. DESIGN: Prospective study. SETTING: Maternity departments of local hospitals in two Italian localities. PATIENT(S): Healthy women who had just given birth in the maternity departments of two local hospitals (n = 679). INTERVENTION(S): Venous blood collection for determination of Hp genotype with the use of starch gel electrophoresis of hemoglobin-supplemented serum. MAIN OUTCOME MEASURE(S): Distribution of Hp genotypes in relation to age of puerperae. RESULT(S): In both populations, the proportion of young mothers was much higher among women who were homozygous for the Hp*1 allele (the Hp*1/*1 genotype) than among women who had other Hp genotypes. In addition, the proportion of multiparous women among the older mothers was higher among those with the Hp*1/*1 genotype than among those with other Hp genotypes. CONCLUSION(S): The data suggest that women with the Hp*1/*1 genotype reproduce at an earlier age and have higher natural fertility potential than women with other Hp genotypes.

Adult↗
PubMed1998

Adenosine deaminase and human reproduction: a comparative study of fertile women and women with recurrent spontaneous abortion.

PROBLEM: We have investigated the possible role of adenosine deaminase (ADA) genetic polymorphism in human fertility through a comparative study of couples with recurrent spontaneous abortion (RSA) and healthy puerperae. METHOD OF STUDY: Adenosine deaminase phenotype has been determined in 209 women with repeated episodes of unexplained spontaneous abortion (RSA) and their husbands, as well as in 115 healthy pregnant women from the population of Rome. An independent sample of 286 puerperae along with their newborn infants in the population of Penne was also studied. RESULTS: The proportion of carriers of ADA*2 allele, which is associated with the lowest enzymatic activity, is lower among women with RSA than among healthy pregnant women from the same population of Rome. Preliminary observations suggest a protective effect of ADA*2 against the development of autoantibodies in RSA. Such an effect seems to be mediated by an interaction with AB0 blood groups. In the population of Penne the proportion of women carrying ADA*2 allele is higher among those who have had two or more previously born children than among women with only one or no children. CONCLUSIONS: The data suggest that women carrying the ADA*2 allele are better protected against the spontaneous loss of embryos and have a higher fertility rate.

ABO Blood-Group System↗
PubMed1998

Phosphotyrosine-protein-phosphatase and diabetic disorders. Further studies on the relationship between low molecular weight acid phosphatase genotype and degree of glycemic control.

We have studied a new sample of 276 NIDDM patients from the population of Penne (Italy). Comparison of the new data with those of 214 diabetic pregnant women from the population of Rome reported in a previous paper has shown that the pattern of association between low molecular weight acid phosphatase genotype and degree of glycemic control is similar in the two classes of diabetic patients. Among nonobese subjects the proportion of ACP1*A (the allele showing the lowest enzymatic activity) is lower in diabetic patients with high glycemic levels (mean value greater than 8.9 mmol/l) than in diabetic patients with a low glycemic level (mean value less than 8.9 mmol/l). Among obese subjects no significant association is observed between glycemic levels and ACP1. Among nonobese subjects the concentration of f isoform of ACP1 is higher in patients showing a high glycemic level than in patients showing a low glycemic level. No significant difference is observed for s isoform.

Acid Phosphatase↗
PubMed1998

The genetics of signal transduction and the feto-maternal relationship. A study of cytosolic low molecular weight phosphotyrosine phosphatase.

Intracellular kinases mediate positive signalling from surface receptors by phosphorylating critical target proteins whereas phosphatases inhibit this process. Differential phosphatase activity at the feto-maternal interface could determine the appropriate relative growth and development on each side of the placenta. The highly polymorphic cytosolic low molecular weight phosphotyrosine-phosphatase (ACP1-cLMWPTPase) has been studied in 170 women who had at least two consecutive spontaneous abortions along with their husbands and in 352 normal puerperae along with their newborn babies. Symmetry analysis of joint wife/husband and mother/infant distribution suggests that when ACP1 activity is lower in the mother than in either her aborted fetus or her child, the probability of abortion is higher and the survival to term is lower as compared to pairs in which the ACP1 activity is higher in the mother than in her fetus. Further analysis has shown that the effect is due to S isoform: i.e. a high mother/fetus S isoform ratio favours intrauterine survival. Analysis of gestational duration and birth weight suggests that a high ACP1 maternal activity coupled with a low or moderate fetal activity favour fetal growth and developmental maturation. The present data indicate that maternal-fetal genetic differences in signal transduction could contribute significantly to variability of intrauterine developmental parameters and to pathological manifestation of pregnancy.

Abortion, Habitual↗
PubMed1997

Low-molecular-weight acid phosphatase (ACP1), obesity, and blood lipid levels in subjects with non-insulin-dependent diabetes mellitus.

Low-molecular-weight acid phosphatase (ACP1) is a polymorphic protein-tyrosine phosphatase present in all human tissues, including adipocytes. A positive association between the low-activity ACP1*A/*A genotype and extreme body mass index has previously been shown by us in obese subjects from the population of Rome. We have now studied a sample of 265 subjects with non-insulin-dependent diabetes mellitus (NIDDM) from another Italian population. There is a significant interaction between ACP1, body mass index, and blood lipid level. A highly significant positive association between ACP1*A/*A and high body mass index similar to that previously observed in obese subjects from the population of Rome is present only in those NIDDM subjects with blood lipid levels within the normal range. In NIDDM subjects the low-activity ACP1*A/*A variant seems to favor the increase of body mass or blood lipid levels or both. The pattern of association is independent of sex, age at survey, age at onset of diabetes, duration of disease, and therapy.

Acid Phosphatase↗