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 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 Sardinia.PTPN22 genotype was determined by DNA analysis.Maternal 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 programs.Three way contingency table analysis was carried out according to Sokal and Rohlf.RESULTS: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 controls.The 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 Sardinia.PTPN22 genotype does not exert significant effect on the age at onset neither in Continental Italy nor and Sardinia.Maternal 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 mothers aging more than 32 years:P=0.062).No effect of sex on age at onset is observed in Continental Italy while in Sardinia female show a lower age at onset of T1D as compared to males(8.07 years in males vs 6.3 years in females:P=0.002).CONCLUSION:The present data confirm the importance of ethnicity on susceptibility and on the age at onset of T1D.

Smoking, ACP₁and Infertility in Subjects with Varicocele

Several studies suggest that smoking may have detrimental effect on seminal parameters and that genetic polymorphisms may influence this effect. In the present paper we have examined the relationship between ACP1 genotypes and the association of smoking and infertility in a sample of men with varicocele. 126 subjects with varicocele were studied. ACP1 genotype was determined by DNA analysis and statistical analyses were performed by SPSS software. In general there is a protective action of low activity *A/*B genotype against infertility that is much more marked in smokers than in non-smokers. If confirmed in other clinical settings, determinations of ACP1 genotype could have practical importance to evaluate the risk of infertility in smokers with varicocele.

Adenylate kinase locus 1 genetic polymorphism and type 2 diabetes

AK1 catalyzes the reversible reaction ATP+AMP ? 2ADP thus contributing to the regulation of relative concentration of these important nu-cleotides. Intracellular ATP is a storage of en-ergy for cellular processes, moreover extracel-lular ATP together with ADP, AMP and adeno-sine are critical signalling molecule for sending messages to nearby cells acting on P1 and P2 receptors. AK1 shows a genetic polymorphism and recently our group has shown that the cor-relation between blood glucose and glycated haemoglobin in T2D is dependent on AK1 phe-notype. In the present paper we have carried further studies on the relationship between AK1 phenotypes and T2D. Possible interactions with ABO blood groups and ACP1 polymorphism have also been investigated. We have re-ex-amined the data on 280 subjects with type 2 diabetes from the White population of Penne (Central Italy). 384 consecutive healthy new-borns from the same population have been also studied. A three way contingency table analysis was carried out according to Sokal and Rohlf and other statistical analyses by SPSS pro-grams. T2D patients with AK12-1 phenotype have higher values of blood glucose level and glycated haemoglobin and an increased ten-dency to dyslipidemia and retinopathy. In addi-tion there is an interaction of AK1 with ABO blood groups and with ACP1 polymorphism. The different activity between AK1 phenotypes could influence the relative concentration of ATP, ADP, AMP and adenosine with important effects on metabolic activity thus explaining the associa-tion of AK1 with clinical manifestation of T2D.

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

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.

Study of geometric parameters for the design of short intakes with fan modelling

The flow over a short intake is characterised by a strong interaction with the fan, that can only be captured when the rotor blades are modelled in the numerical simulations. In this paper, we use a coupled methodology to derive indications about relevant geometric variables affecting the high-incidence operation of an ultra-high bypass ratio turbofan intake with a length-to-diameter ratio of 0.35. By reproducing the effect of the fan through a body force model, we carry out a parametric study of the influence of the contraction ratio and the scarf angle at take-off conditions for a grid of 28 different three-dimensional shapes. The analysis of the selected performance metrics distributions at three angles of attack of 16., 24., and 28. reveals that a contraction ratio higher than 1.20 is needed to avoid separation at high incidence. While for an attached inlet the best performance is found with a moderate scarf angle, in presence of a developed separation the distortion level reduces as the scarf decreases up to negative values. We discuss the correspondence between the distortion indexes and the flow field, highlighting the origin of the detachment for the different geometries, according to the operating condition, and analysing the fan operation in the most distorted case. Finally, we assess the influence of modelling the rotor in the simulations, showing that its suppression effect on the separation at a given incidence depends on the intake geometric features.