Allergy and Uterine Leiomyomas: Cooperative Interaction with ACP1 Genetic Polymorphism.

Background: The possible association between allergy and neoplastic disorders has been the subject of many investigations but no general relationship has been determined. Little attention, however, has been paid to the possible role of allergy in the clinical manifestations of these diseases. In this study, the role of allergy in the susceptibility to uterine leiomyomas and in their growth was investigated.

Genetic variability within Adenosine Deaminase gene and uterine leiomyomas.

Objective: The recent observation of an association of colon cancer with two polymorphic sites within the Adenosine Deaminase (ADA) gene suggests an involvement of these polymorphisms in the development of solid tumors. This prompted us to search for a similar association in uterine leiomyomas.

Study Design: We have studied 181 women admitted to the hospital for leiomyomas requiring surgical intervention and 248 women of comparable age without clinical signs of leiomyomas.

The effect of ACP1, ADA6 and PTPN22 genetic polymorphisms on the association between p53 codon 72 polymorphism and endometriosis.

Purpose: Association between p53 codon 72 and endometriosis has been observed in populations of East Asia but not in those of European descent. Genetic polymorphisms could interact with p53 codon 72 influencing its association with endometriosis, thus explaining these differences among populations.

Methods: 130 women hospitalized for endometriosis and a sample of 250 women without endometriosis have been studied.

PTPN22 and uterine leiomyomas.

Objective: It has been suggested that the development of uterine leiomyomas is positively influenced by an immune system in a chronically inflammatory state and that a lower level of regulating T cell (Treg cells) would play a central role. Since it has been suggested that the W620 variant of protein tyrosine phosphatase non-receptor type 22 (PTPN22) decreases the number of Treg cells, we investigated a possible relationship between PTPN22 polymorphism and uterine leiomyomas.

Study Design: We studied 203 white women from Rome who were hospitalized for symptomatic leiomyomas requiring surgical intervention.

Study of factors influencing susceptibility and age at onset of type 1 diabetes: A review of data from Continental Italy and Sardinia.

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.

Effect of genetic factors on the association between coronary artery disease and PTPN22 polymorphism.

PTPN22 has been previously found associated with coronary artery disease (CAD). In the present note we have studied the effect of p53 codon 72, acid phosphatse locus 1 (ACP1) and adenosine deaminase (ADA) genetic polymorphism on the strength of association between PTPN22 and CAD. We have studied 133 non diabetic subjects with CAD, 122 non diabetic cardiovascular patients without CAD and 269 healthy blood donors.

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.

p53 Codon 72 Genetic Polymorphism in Asthmatic Children: Evidence of Interaction With Acid Phosphatase Locus 1.

Several lines of evidence are implicating an increased persistence of apoptotic cells in patients with asthma. This is largely due to a combination of inhibition, or defects in the apoptotic process and/or impaired apoptotic cell removal mechanisms. Among apoptosis-inducing genes, an important role is played by p53.

Coronary artery disease. A study of three polymorphic sites of adenosine deaminase gene.

Objectives: The role of adenosine as a cardioprotective agent is well known and recent experimental studies suggest that impairment of adenosine-related signal transduction contributes to the pathophysiology of chronic heart failure. The recent observation of an association between ADA, genetic polymorphism and coronary artery disease (CAD) prompted us to study the possible relevance of three intragenic polymorphic sites of the ADA gene (ADA1, ADA2 and ADA6).

Methods And Results: 136 non-diabetic patients with coronary artery disease and 246 healthy blood donors from the white Italian population of Central Italy and 129 non-diabetic patients with CAD and 204 newborns from the white Polish population were studied.

ACP1 Genetic Polymorphism and Coronary Artery Disease: Evidence of Effects on Clinical Parameters of Cardiac Function.

Background: Kinases and phosphatases have an important role in the susceptibility and clinical variability of cardiac diseases. We have recently reported an association between a phosphoprotein phosphatase controlled by Acid Phosphatase locus 1 (ACP1), and Coronary artery disease (CAD) suggesting an effect on the susceptibility to this disease. In the present note we have investigated a possible role of ACP1 in the variability of clinical parameters of cardiac function.

p53 codon 72 polymorphism and coronary artery disease: evidence of interaction with ACP₁.

Background: Common biological features between cancer and atherosclerosis suggest possible association of p53 with atherosclerotic diseases, but data on such a relationship are controversial, suggesting interactions with other variables. Acid phosphatase locus 1 (ACPACP₁) is a polymorphic gene that controls the synthesis of an enzyme involved in important metabolic functions. Since ACPACP₁ is associated with coronary artery disease (CAD), we searched for possible interactions between this enzyme and p53 codon 72 polymorphism with regard to their effects on susceptibility to CAD.

Acid phosphatase locus 1 genetic polymorphism and cancer grading.

Background: Currently, there is a surge of interest on the possible relationship between cancer and acid phosphatase locus 1 (ACP(1)), an enzyme involved in the modulation of growth factors and cellular metabolism. As far as the authors know, the possible relationship between ACP(1) genetic variability and cancer grading has not yet been considered. In this article, the authors have studied the relationship between ACP(1) genotype and grade in colon and endometrium cancers.

Effect of ADA1 mother-fetus and wife-husband phenotypic differences on the ratio birth weight/placental weight in fertile women and on reproductive success in couples with RSA.

Objectives: To study the effect Adenosine Deaminase locus 1 (ADA(1)) mother-fetus and wife-husband phenotypic differences on the ratio Birth Weight/Placental Weight (BW/PW) in fertile women and on reproductive success in couples with repeated spontaneous abortion (RSA).

Methods: 209 couples with primary RSA and a consecutive series of 379 healthy puerperae with their newborn infants from the White Caucasian population of central Italy were studied. In primary RSA women reproductive success was indicated by the presence of at least one live-born infant within 5 years of follow up.

Functional polymorphisms of GSTA1 and GSTO2 genes associated with asthma in Italian children.

Background: Asthma is an airway disorder characterized by bronchial inflammation. An imbalance between the oxidative forces and the antioxidant defense systems has been implicated in the pathogenesis of asthma. Glutathione S-transferases (GSTs) play an important role in cellular protection against inflammation.

Genotypes of p53 codon 72 correlate with age at onset of type 1 diabetes in a sex-specific manner.

In type 1 diabetes mellitus (T1D) p53 pathways are up-regulated and there is an increased susceptibility to apoptosis. The hypothesis is that p53 codon 72 polymorphism could be associated with T1D. A total of 286 children with T1D and a control sample of 730 subjects were studied.

p53 codon 72 polymorphism and coronary artery disease: evidence of association with left ventricular ejection fraction.

Introduction: Recently, there has been a surge of interest on the possible relationship between p53 polymorphism and coronary atherosclerosis. The authors have investigated the possible association of p53 codon 72 polymorphism with left ventricular ejection fraction (LVEF) in subjects with and without coronary artery disease (CAD).

Methods: The authors have studied 198 subjects admitted consecutively to Valmontone Hospital for CAD and 129 subjects admitted for cardiovascular diseases without CAD.

Adenylate kinase locus 1 polymorphism and feto-placental development.

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 (AK₁) 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.

Isolated left ventricular noncompaction in a case of sotos syndrome: a casual or causal link?

A 16-year-old boy affected by Sotos syndrome was referred to our clinic for cardiac evaluation in order to play noncompetitive sport. Physical examination was negative for major cardiac abnormalities and rest electrocardiogram detected only minor repolarization anomalies. Transthoracic echocardiography showed left ventricular wall thickening and apical trabeculations with deep intertrabecular recesses, fulfilling criteria for isolated left ventricular noncompaction (ILVNC).

A Case of Isolated Left Ventricular Noncompaction with Basal ECG-Tracing Strongly Suggestive for Type-2 Brugada Syndrome.

Isolated left ventricular noncompaction (ILVNC) is a cardiomyopathy caused by intrauterine arrest of compaction of the myocardial fibres and meshwork, an important process in myocardial development. ILVNC is clinically accompanied by depressed ventricular function, arrhythmias, and systemic embolization. We reported a case of ILVNC with basal ECG-tracing strongly suggestive for type-2 Brugada syndrome (BrS).

PTPN22 1858C>T (R620W) functional polymorphism and human longevity.

The PTPN22 gene, located on chromosome 1p13, encoding lymphoid protein tyrosine phosphatase (LYP), plays a crucial role in the negative control of T lymphocyte activation. Since the age-related change in T-cell signal transduction may be one of the most important causes of cell-mediated immune response decline with ageing, we performed a population-based association study to test whether the PTPN22 1858C>T (R620W) functional polymorphism affects the ability to survive to old age and to reach even exceptional life expectancy. 892 unrelated healthy individuals (age range 8-106 years, 403 males and 489 females) from central Italy were studied.

Is there a role of ACP1-ADA1 genetic complex in immune reaction? Association with T1D and with past malarial morbidity.

In this article, we confirm the positive association of acid phosphatase locus 1 (ACP1)*A/adenosine deaminase locus 1 (ADA1)*2 gametic type with type 1 diabetes (T1D) previously reported and show a negative correlation between the frequency of this gametic type with past malarial morbidity in Sardinia. One hundred seven adult women with T1D and 385 healthy adult women from the Caucasian population of Central Italy have been studied. Data on 1384 children from the central area of Sardinia have also been reexamined.

The interaction of ACP1, ADA1, diabetes and gender in coronary artery disease.

Introduction: Previous separate studies have shown associations of coronary artery disease (CAD) with acid phosphatase locus 1 (ACP1) and adenosine deaminase locus 1 (ADA1) genetic polymorphisms. Because it is known that the 2 systems interact and have important immunologic and metabolic functions, these 2 genes were both examined in the same sets of subjects.

Method: Two-hundred forty subjects with CAD, 156 subjects with cardiovascular diseases without CAD, 279 subjects with Non Insulin Dependent Diabetes Mellitus (NIDDM) without CAD and 771 consecutive healthy newborn infants have been studied.

Autoimmune-associated PTPN22 R620W variation reduces phosphorylation of lymphoid phosphatase on an inhibitory tyrosine residue.

A missense C1858T single nucleotide polymorphism in the PTPN22 gene recently emerged as a major risk factor for human autoimmunity. PTPN22 encodes the lymphoid tyrosine phosphatase (LYP), which forms a complex with the kinase Csk and is a critical negative regulator of signaling through the T cell receptor. The C1858T single nucleotide polymorphism results in the LYP-R620W variation within the LYP-Csk interaction motif.

Type 1 diabetes: evidence of interaction between ACP1 and ADA1 gene polymorphisms.

Background: ACP1 (acid phosphatase locus 1, a cytosolic low-molecular-weight phosphotyrosin phosphatase) and ADA1 (adenosine deaminase locus 1) are two polymorphic systems involved in immune reactions. Observed interactions at the biochemical and clinical levels between the two systems prompted this investigation of a possible interaction concerning susceptibility to type 1 diabetes.

Material/methods: Two hundred eighty-seven children admitted consecutively to the hospital for type 1 diabetes and 727 healthy newborn infants were studied.

Birth weight and coronary artery disease. The effect of gender and diabetes.

Background: The developmental origin theory of coronary heart disease proposes that undernutrition in utero permanently changes body functions and metabolism leading to an increased risk of coronary artery diseases (CAD) in adult life. Some studies support this theory but others suggest that birth weight (BW) is not a major risk factor for cardiovascular diseases. Gender differences concerning the association between BW and risk factors for CAD have been reported in some studies but not in others.