Maria Banci

ACP1 genetic polymorphism and coronary artery disease: an association study.

Objectives: Assuming an immune component in the pathogenesis of atherosclerosis, we have investigated a possible association between coronary artery disease (CAD) and the acid phosphatase locus 1 (ACP1) genetic polymorphism, which has previously been found to be associated with immune disorders. Methods: 226 subjects admitted to the hospital for CAD, 358 consecutive newborn infants, 279 adult subjects with type 2 diabetes without CAD and 137 adults without diabetes and without CAD from the Caucasian population of Rome were studied. The ACP1 genotype was determined by DNA analysis. Statistical analyses were performed using the SPSS package. Results: CAD females showed an excess of ACP1 *A/*C and *B/*C genotypes and a deficiency of ACP1 *B/*B genotype compared to controls, while CAD males did not show significant differences. Among diabetic women the proportion of *C allele carriers was much greater in those with CAD than in those without CAD. This difference was much less evident in nondiabetic women. Conclusion: ACP1 may be involved in susceptibility to CAD. Since ACP1 has been found to be associated with immunological diseases, our observation reinforces the notion of an immune component in the pathogenesis of atherosclerosis.

Adenosine Deaminase Genetic Polymorphism and Coronary Artery Disease

in the Polish sample the great majority of patients are males. We have also found that the proportion of ADA * 2 allele in subjects with CAD decreases with age. Differences The role of adenosine as a cardioprotective agent is well known [1] and recent experimental studies suggest that impairment of adenosine-related signal transduction contributes to the pathophysiology of chronic heart failure [2] . Thus the recent observations by Safranow et at. [3] of a reduced proportion of ADA * 2 allele of adenosine deaminase (ADA) gene in subjects with coronary artery disease (CAD) appear very interesting and prompted us to search for a confirmation in our population. ADA catalyzes the irreversible deamination of adenosine in inosine and ADA * 2 allele is about 30% less active than ADA * 1 allele. We studied 200 patients with CAD and 771 consecutive healthy newborns from the same Caucasian population. Patients or their parents gave consent for participation in the study that was approved by the IRB. The ADA genotype was determined by DNA analysis as previously described [4] . Figure 1 shows the proportion of ADA * 2 allele in subjects with CAD and in controls separately for males and females. A negative association between CAD and ADA * 2 allele is only present in males. Gender differences are frequently found in association studies and are explained by differences in the hormonal pattern. In our sample the number of males is slightly greater than that of females, while Received: March 12, 2008 Accepted: March 14, 2008 Published online: June 18, 2008

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

Summary 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 (ACP1) is a polymorphic gene that controls the synthesis of an enzyme involved in important metabolic functions. Since ACP1 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. Material/Methods The study included 381 patients admitted to the hospital for cardiovascular disease (232 patients with CAD and 149 with other cardiovascular problems) and 97 healthy newborns. Results The proportion of subjects carrying the *Pro allele of p53 codon 72 and the high activity *B*C genotype of ACP1 is higher in CAD (10.3%) than in non-CAD patients (2.0%) and in healthy newborns (6.2%). Conclusions The data suggest an interaction between p53 codon 72 and ACP1 wherein a positive effect of the p53 *Pro allele on susceptibility to CAD occurs, but only in the presence of the ACP1 genotype characterized by high enzymatic activity.

Coronary artery disease: evidence of interaction between PTPN22 and p53 genetic polymorphisms.

Objectives: We recently reported an association between the PTPN22 genetic polymorphism and coronary artery disease (CAD) in nondiabetic subjects. Since recent studies suggest that p53 may be involved in coronary atherosclerosis, we have investigated a possible interaction between PTPN22 and p53 codon 72 genetic polymorphisms regarding their effects on susceptibility to CAD in nondiabetic subjects. Methods: The genotypes of p53 codon 72 and PTPN22 were determined by DNA analysis in 128 nondiabetic subjects with CAD, 122 healthy blood donors and 117 nondiabetic subjects with cardiovascular diseases without CAD. Results: In subjects with the *Arg/*Arg genotype of p53 codon 72, no association was observed between CAD and PTPN22. However, this association was very strong in subjects carrying the *Pro allele of p53 codon 72. Subjects carrying both the *T allele of PTPN22 and the *Pro allele of p53 were overrepresented in CAD nondiabetic cases relative to the other two groups (p = 0.001). Conclusions: Since both p53 and PTPN22 are involved in autoimmune inflammation, an interaction between the two systems appears biologically plausible. In the analysis of multifactorial disorders, the simultaneous analysis of multiple genes functionally related to diseases will provide a more productive approach than studies of single genetic factors performed from a Mendelian perspective.

Atherosclerosis and PTPN22: A Study in Coronary Artery Disease

Objectives: Recently, it has been shown that PTPN22 genetic polymorphism is associated with phenotypes related to the risk of atherosclerosis. In the present note, we have searched for a possible association of PTPN22 polymorphism with coronary artery disease (CAD). Methods: One hundred and thirty-four non-diabetic subjects admitted to hospital for CAD and 174 healthy subjects (blood donors) were studied. PTPN22 genotypes were determined by DNA analysis. Statistical analyses were performed by SPSS programs. Results: In CAD patients, the proportion of carriers of the *T allele of PTPN22 is significantly higher compared to healthy controls (OR 2.66; 95% CI 1.07–6.72). Conclusions: The present observation confirms the association of PTPN22 phenotype with atherosclerosis and suggests a role of immune mechanism in the pathogenesis of CAD.

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. Fifty-nine subjects admitted for CAD to Division of Cardiac Surgery of Tor Vergata University were also studied. All subjects were from the white population. The p53 polymorphism was evaluated using the restriction fragment length polymorphism polymerase chain reaction. Results:p53 codon 72 polymorphism is a significant independent predictor of LVEF in subjects with CAD but not in subjects with cardiovascular disease without CAD. In subjects with CAD, LVEF is significantly lower in subjects carrying the *Pro variant than in *Arg/*Arg subjects. This effect is more evident in subjects with a positive history of infarction. Conclusions:Our study points to a significant relationship of p53 codon 72 polymorphism with cardiac function in subjects with CAD.

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). Some sporadic forms of ILVNC are reported to be caused by a mutation on CSX gene, mapping on chromosome 5q35. To our knowledge, this is the first report of a patient affected simultaneously by Sotos syndrome and ILVNC.

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. Results:The association of ACP1 and ADA1 with CAD depends on sex and diabetes. In particular, the association between ADA1 and CAD is present in nondiabetic subjects only, and it is dependent on sex (males), whereas the association of CAD with ACP1 is present in diabetic subjects only, and it is dependent on sex (females). Conclusions:The fact that the association of ACP1 with CAD is evident only in diabetic subjects, whereas the association of ADA1 with CAD is evident only in nondiabetic subjects suggests an heterogeneity in the pathogenetic mechanisms leading to CAD. In addition, the association with sex that could be based on hormonal differences is in favor of heterogenity.

Coronary Artery Disease: A Study on the Joint Role of Birth Weight, Adenosine Deaminase, and Gender

An inverse relationship between birth weight and coronary artery diseases is well documented but it remains unclear which exposure in early life might underlie such association. Recently it has been reported an association between adenosine deaminase genetic polymorphism and coronary artery diseases. Gender differences in the degree of this association have been also observed. These observations prompted us to study the possible joint effects of BW, ADA, and gender on the susceptibility to coronary artery diseases. 222 subjects admitted to hospital for nonfatal coronary artery diseases, and 762 healthy consecutive newborns were studied. ADA genotypes were determined by DNA analysis. A highly significant complex relationship has emerged among ADA, birth weight, and gender concerning their role on susceptibility to coronary artery diseases in adult life. Odds ratio analysis suggests that low birth weight is more important in females than in males. ADA∗2 allele appears protective in males, while in females such effect is obscured by birth weight.

Smoking and Hypertension: A Study in Subjects Admitted to Hospital for Cardiovascular Diseases

Aims: There is a general consensus in considering cigarette smoking as a major risk factor for cardiovascular diseases: a direct causal association between smoking and hypertension however is questioned. The present paper reports a study on the effect of cigarette smoking and of other clinical parameters on hypertension in a sample of subjects admitted to Hospital for Cardiovascular Diseases (CVD). Study Design: Observational study. Place and Duration of Study: Department of Cardiology Valmontone Hospital and Department of Biomedicine and Prevention, University of Rome Tor Vergata, between April 2007December 2013. Methodology: We have studied 335 subjects admitted to the Hospital for Cardiovascular Diseases. Statistical analyses were in the study that was approved by the Ethical Committee. We have considered hypertension in relation to smoking, diabetes, age and sex. Results: Multivariate statistical analyses have shown a high significant effect of age Original Research Article Banci et al; CA, 2(4): 325-331, 2014; Article no. CA.2014.4.018 326 (P<.001) and diabetes (P<.01) on hypertension and a border line effect of smoke (P=.05). No effect of sex has been detected (P=.47). The proportion of subjects with hypertension is positively correlated with the number of risk factors examined. Conclusion: Our data indicate that an independent effect of smoking on blood pressure is relatively small and suggest an additive effect of the variables considered on the risk of hypertension.