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

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World Journal of Cardiology 2014年第6期6卷 376-380页

作者： Fulvia Gloria-bottini Patrizia Saccucci Maria Banci Paolo Nardi Mattia Scognamiglio Antonio Pellegrino egidio bottini Luigi Chiariello Department of Biomedicine and Prevention School of MedicineUniversity of Rome Tor Vergata00133 RomeItaly Department of Cardiology Valmontone Hospital Department of Cardiac Surgery University of Rome Tor VergataSchool of Medicine

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. Informed written consent was obtained from all subjects and the study was approved by the Ethical Committee. A high significant association between PTPN22 and CAD is observed in carriers of *A allele of ACP1 with a higher proportion of *T allele carriers in non diabetic subjects with CAD as compared to controls and to non diabetic subjects with cardiovascular diseasewithout CAD. A similar pattern is observed in carriers of *Pro allele of p53 codon 72 with a higher proportion of *T allele carriers in non diabetic subjects with CAD as compared to other groups. A highly significant association between PTPN22 and CAD is observed in carriers of ADA2 *2 allele with higher proportion of *T allele carriers in non diabetic subjects with CAD as compared to other group. There is a high significant correlation between the number of factors that contributes to increase the strength of association between PTPN22 *T and CAD and the proportion of *T carriers in CAD. ACP1,p53 codon 72 and ADA are involved in immune reaction and give an important additive contribution to the strength of association between PTPN22 and CAD. This study stresses the importance of the simultaneous analysis of multiple genes functionally related to a specific disease: the approach may give important hints to understand multifactorial disorders.

关键词： Coronary artery disease PTPN22 Acid phosphatse locus 1 Adenosine deaminase 2 p53 codon 72

The association of adenosine deaminase with coronary artery disease: Effect of gender and diabetes

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Health 2013年第2期5卷 166-169页

作者： Fulvia Gloria-bottini Krzysztof Safranow Maria Banci Agnieszka Binczak-Kuleta Patrizia Saccucci Andrzej Ciechanowicz Andrea Magrini Zdzislawa Kornacewicz-Jach egidio bottini Dariusz Chlubek Department of Biochemistry and Medical Chemistry Pomeranian Medical University Szczecin Poland Department of Biomedicine and Prevention School of Medicine University of Rome Tor Vergata Rome Italy Department of Cardiology Pomeranian Medical University Szczecin Poland Department of Cardiology Valmontone Hospital Valmontone Italy Department of Laboratory Diagnostics and Molecular Medicine Pomeranian Medical University Szczecin Poland

An association between ADA1 and Coronary Artery Disease (CAD) has been observed in Polish and in Italian populations but in Italian population the association was present in males only. In order to enlighten these differences we have carried out a collaborative study in the two populations. In Italy 215 subjects admitted to the Hospital for CAD, 275 subjects with Type 2 Diabetes (T2D) without CAD and 398 healthy new-borns were studied. In Poland 173 subjects with CAD and 200 healthy newborns were studied. Written informed consent was obtained from all subjects or from their mothers to participate to the study that was approved by the I.R.B. ADA1 polymorphism was determined by DNA analysis. Three way contingency table analysis was performed by a log linear model. The association between CAD and ADA1 is present in non diabetic male subjects only: OR = 0.195, p = 0.007 in the Italian population and OR = 0.163, p = 0.004 in the Polish population. The data suggest a significant role of immunological mechanisms in the pathogenesis of CAD without diabetes. Gender differences in immune diseases could explain the lack of association in females.

关键词： ADA CAD Gender Diabetes

Adenylate kinase locus 1 genetic polymorphism and type 2 diabetes

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

Health（健康） 2011年第2期 77-81页

作者： Fulvia Gloria-bottini Elena Antonacci Anna Neri Andrea Magrini egidio bottini

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World Journal of Diabetes 2014年第4期5卷 557-561页

作者： Fulvia Gloria-bottini Patrizia Saccucci Gian Franco Meloni Maria Luisa Manca-Bitti Luca Coppeta Anna Neri Andrea Magrini bottini egidio Department of Biomedi-cine and Prevention School of Medicine University of Rome Tor Vergata 00133 Rome Italy Department of Pediatrics University of Sassari Medical School 07010 Sassari Italy Pediatric Diabetology and Endocrinol-ogy Unit Policlinico Tor Vergata University Hospital 00144 Rome Italy

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 ***:Three hundred seventy six subjects admitted consecutively to the hospital for T1D and 1032healthy 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 ***22 genotype was determined by DNA *** 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 *** way contingency table analysis was carried out according to Sokal and ***:The pattern of association between PTPN22and T1D is similar in Continental Italy and Sardinia:the proportion of*T allele carriers is 13.6%in T1D vs6.7%in controls in Continental Italy while in Sardinia is 7.3%in T1D vs 4.4%in *** 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 is89.3%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 ***22 genotype does not exert significant effect on the age at onset neither in Continental Italy nor and *** age does not influence significantly age at onset in Italy(8.2 years in T1D infants from mothers aging32 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 vs7.54 years in T1D infants from mo

关键词： Type 1 diabetes Continental Italy Sardinia Protein tyrosin phosphatase 22 Maternal age Age of onset Sex