187,483 research outputs found
Type 2 diabetes and the genetics of signal transduction: a study of interaction between adenosine deaminase and acid phosphatase locus 1 polymorphisms
No full textAcid phosphatase locus 1 (ACP1) is a highly polymorphic enzyme that has an important role in flavoenzyme activity and in the control of insulin receptor activity and band 3 protein phosphorylation status. Adenosine deaminase (ADA) is a polymorphic enzyme that catalyses the irreversible deamination of adenosine to inosine and has an important role in regulating adenosine concentration. Based on the hypothesis that ACP1 counteracts insulin signaling by dephosphorylating the insulin receptor and that adenosine has an anti-insulin action, we reasoned that low ACP1 activity (low dephosphorylating action on insulin receptor) when associated with high ADA activity (low adenosine concentration) would result in a cumulative effect towards an increased glucose tolerance. On the contrary, high ACP1 activity when associated with low ADA activity would result in a cumulative effect towards a decreased glucose tolerance. A total of 280 adult subjects with type 2 diabetes from the population of Penne (Italy) were studied. There was a nonsignificant trend toward an increase in the proportion of subjects with the complex type with high ACP1 activity and low ADA activity (ie, *B/*B; *A/*C; *B/*C; *C/*C//ADA*1/*2 and *2/*2) in type 2 diabetes relative to that observed in newborn infants from the same population. High ACP1 activity/low ADA activity joint genotype was positively associated with high glycemic levels and with high body mass index (BMI) values. Low ACP1 activity/high ADA activity joint genotype was also positively associated with dyslipidemia. These findings suggest that both ACP1 and ADA contribute to the clinical manifestations of type 2 diabetes and probably also have a marginal influence on susceptibility to the disease. Both additive and epistatic interactions between the 2 systems seem to be operative
How the vestibular system modulates tactile perception in normal subjects: a behavioural and physiological study
No full textCaloric vestibular stimulation (CVS) is a physiological technique demonstrated to transiently improve hemianaesthesia in right brain-damaged patients (Bottini et al. in Exp Brain Res 99(1):164-169, 1994, Nature 376:778-781, 1995, Neurology 65(8):1278-1283, 2005). Recent studies suggest that these effects are based on the anatomical overlapping between vestibular and tactile projections (Bottini et al. in Nature 376:778-781, 1995) in the human brain. However, much less is known about behavioural effects of this manipulation on normal subjects. We aimed to explore tactile perception during left ear CVS in normal subjects. We administered seventeen right-handed normal subjects with different types of tactile stimuli (above and below threshold) during left ear CVS. To further ensure standardized procedure, tactile stimulation was delivered through a tool-developed ad hoc for the experiment. The experiment was divided in 3 conditions: (1) Baseline, (2) PostCVS and (3) Delayed CVS. We found a main effect of stimulus type (F ((2,32)) = 907.712; P = 0.000) and condition (F ((2,32)) = 55.505; P = 0.000). Moreover, post hoc comparisons revealed that below threshold stimuli are most affected by CVS (t ((16)) = -11.213; P = 0.000). Left ear CVS modulates tactile perception also in normal subjects. Moreover, this modulation seems to be selective for below threshold stimuli and not caused by attentive processes. A multisensory phenomenon is possibly the best explanation for this interaction between touch and vestibular systems, corroborated also by the anatomical evidence and by the previous knowledge about interaction with the environment
Acid phosphatase locus 1 (ACP1): Possible relationship of allelic variation to body size and human population adaptation to thermal stress - A theoretical perspective
No full textThe acid phosphatase locus 1 (ACP1) codes for a low molecular weight phosphotyrosine protein phosphatase that has the important action of dephosphorylating tyrosine phosphorylated proteins and peptides and a second important role in modulating flavin cofactor levels and the activity of flavo-enzymes. These functions significantly influence cell division, differentiation, and growth. Two alleles (ACP1*A and ACP1*B) reach polymorphic frequencies at the ACP1 locus in all human populations, while the ACP1*C and ACP1*R alleles reach polymorphic frequencies in restricted geographical regions. The worldwide distribution of these alleles, and data from several clinical studies, strongly suggest that the ACP1 locus functions to modulate growth and that selection at this locus is a component of the selective processes influencing body mass and human population adaptation to thermal stress. The ACP1*A allele reaches highest frequencies at extreme latitudes and appears to be associated with maximizing body mass and adaptation to cold stress, whereas the ACP1*B allele reaches highest frequencies in tropical and subtropical environments and appears to be associated with minimizing body mass and adaptation to heat stress. The high frequency of the ACP1*C allele at northern latitudes, where ACP1*A allele frequencies are elevated, may be a mechanism for limiting fetal and maternal complications associated with fetal macrosomia and adult obesity in populations where protein and calorie intake are relatively hig
Further Observations on Associations Between the ADA Gene and Past Malaria Morbidity in Sardinia.
No full textObjectives: 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. We have now studied
the ADA2 locus, another polymorphic site with two alleles ADA2 *1 and ADA2 *2 within the ADA gene.
Methods: In the area of Oristano (where malaria was endemic in the past) 51 consecutive newborns and in the area
of Nuoro (where malaria was not as endemic) 48 consecutive newborns were examined.
ADA1 and ADA2 genotypes were determined by DNA analysis.
Results: The low frequency of the ADA1*2 allele in the area where malaria was endemic is confirmed. The frequency
of the ADA2*2 allele is higher in Oristano than in Nuoro resulting in a higher frequency of the ADA1*1/ADA2*2 haplotype
in Oristano as compared to Nuoro. This suggests a selective advantage of this haplotype in a malarial
environment.
Conclusions: The ADA gene shows other polymorphic sites further studies on their role in human adaptation to
malaria could be rewarding
A study of human growth hormone and insulin gene regions in relation to metabolic control of non-insulin-dependent diabetes mellitus
No full textThe possible association of human growth hormone (hGH) and insulin (INS) gene regions with metabolic control in diabetes was investigated in 98 subjects with non-insulin-dependent diabetes mellitus (NIDDM); 54 control subjects from the same population were also studied. Two polymorphic restriction sites in the region of the hGH cluster (BGLIIA and BGLIIB) show significant association with both glycemic and hemoglobin A1c (HbA1c) levels. Mean values for plasma glucose and HbA1c show a maximum in the BGLIIA *1/*1 genotype and a minimum in the BGLIIA *2/*2 genotype. Mean values for plasma glucose and HbA1c show a maximum in the BGLIIB *1/*2 genotype. The BGLIIA*2/BGLIIB*1 haplotype shows a negative correlation with plasma glucose and HbA1c levels. Since the two markers are located in the area surrounding the hGH-V locus, the expression of this gene in NIDDM warrants further investigatio
Association of the ACP1 genotype with metabolic parameters upon initial diagnosis of type 1 diabetes.
No full textBACKGROUND:
ACP1, also called cLMWPTP (cytosolic Low Molecular Weight PTPase) is a highly polymorphic enzyme involved in the modulation of signal transduction by insulin, PDGF receptors, and T-cell receptors. The enzyme is controlled by a locus on chromosome 2, with three common codominant alleles; the corresponding six genotypes show strong variations in total enzymatic activity. The purpose of our research was to determine the relationship of ACP1 with glycemic level, ketoacidosis and HbA1C in children with Type 1 diabetes.
MATERIAL/METHODS:
We studied 189 consecutive children with Type 1 diabetes, from the Pediatric Clinic of Sassari University. The ACP1 genotype was determined by PCR and digestion by specific restriction enzymes.
RESULTS:
At initial diagnosis a strong negative correlation was observed between glycemic level and ACP1 activity, with the highest levels in genotypes with low activity. Ketoacidosis and HbA1C show a similar pattern of relationship with ACP1. A comparative analysis of the data on Type 1 diabetes with previously obtained data on Type 2 diabetes shows an opposite pattern of relationship between ACP1 and metabolic parameters. Moreover, correlation between glycemia and HbA1C in Type 1 diabetes is much weaker than in Type 2 diabetes.
CONCLUSIONS:
These differences suggest that the enzyme might be involved in different signal transduction pathways relevant in the pathogenesis of these two classes of diabetic disorders. It would be interesting to study the possible correlation in Type 1 diabetes between ACP1 and immunological parameters
P 53 codon 72 and past malaria morbidity in Sardinia
No full textInfection of liver cells is the first stage of malaria: parasites replicate inside the cells and then invade erythrocytes. Apoptosis mechanism in liver cells is triggered by the growth of parasites: this provides a release of parasite antigen that initiates a protective immune response. On the other hand, the parasite interferes with cell apoptosis mechanism resulting in resistance to apoptosis and successful infection [1-3]. Recently it has been observed that p53 pathway is involved in parasite survival, increased level of p53 reduces the liver parasite load whereas p53 knockout mice suffers increased liver load [4].The p53 codon 72 is characterized by a polymorphism in exon 4 with CGC to CCC transition (rs1042522) that confers a change of arginine to proline in amino acid sequence of protein [5]. Amino acid change affects biochemical and functional properties of p53 protein. The arginine variant is a stronger apoptosis inducer while the proline variant is a stronger transcriptional activator [6].Since apoptosis of liver cells seems to have a protective effect against malaria one would expect a positive selection of *Arg allele in areas of heavy malaria endemia.We have studied 46 consecutive newborn infants from Oristano area of Sardinia and 47 cosecutive newborn infants from area of Nuoro. Oristano was in the past a heavy malaria endemic area whereas the endemia was very light in Nuoro area. Blood was collected from the placental side of umbilical vein after cord section. Written informed consent was obtained by parents to participate to the study that was approved by I.R.B. p53 codon 72 genotypes were determined by DNA analysis as previously described [7].Figure 1 shows the proportion of p53 codon 72 genotypes in Nuoro and Oristano areas: *Arg/*Arg genotype is much more frequent in Oristano than in Nuoro (p=0.024). The frequency of *Arg allele is 82.6% in Oristano and 69.1% in Nuoro (p=0.04).In accordance with experimental studies suggesting apoptosis of the liver cells as a defense mechanism against parasite invasion, *Arg allele favoring apoptosis seems to have been selected positively in area of Sardinia exposed in the past to heavy malaria endemia
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