Adenosine Deaminase Polymorphism Research Articles

A Functional Adenosine Deaminase Polymorphism Associates with Evening Melatonin Levels and Sleep Quality.

Increased adenosine levels throughout the day promote sleepiness. A single nucleotide polymorphism (SNP) in the adenosine deaminase ADA gene (rs73598374) has been shown to affect sleep regulation. The extent to which lower ADA enzymatic activity is associated with the homeostatic sleep factor, melatonin, is uncertain. To test this possibility, we assessed the relationship between the ADA polymorphism and evening melatonin levels, as well as self-reported sleep behavior. Given the close relationship between mood and sleep behavior, we further tested the impact of ADA genotype on self-reported mood. We show that relative to the GG homozygotes, the A allele carriers (higher adenosine levels) had significantly higher evening melatonin levels as well as significantly better sleep quality. We further show the correlations between sleep and mood measures were altered by ADA genotype, with a stronger relationship observed in the GG (lower adenosine) group. Combined, these findings advance our understanding of the biochemistry of melatonin production by showing that there is a relationship between ADA genotype and melatonin levels. The differential relationships between sleep and psychological health between the genotype groups may reveal novel insights about the development of genotype-specific progression of various psychological disorders such as chronic anxiety and stress.

Genetic polymorphisms associated with polycystic ovary syndrome among Iranian women

Polycystic ovary syndrome (PCOS) involves abnormalities in ovarian, reproductive, and metabolic systems. Genetic polymorphisms associated with individual differences and variations might be related to complex disorders with unknown causes, including PCOS. Several leading genetic markers with known cellular functions have been identified among Iranian women presenting with PCOS. In particular, the existing evidence shows a significant relationship between PCOS and the following genetic polymorphisms: rs2275913 (interleukin-17A), rs9927163 (interleukin-32), Pro12Ala (peroxisome proliferator-activated receptor-γ), rs17173608 (chemerin), rs2236242 (vaspin), ApaI (vitamin D receptor), and rs7895833 (sirtuin 1). In addition, a higher risk of PCOS is associated with the rs2910164 (microRNA 146a), rs2241766 (adiponectin), -34T/C (cytochrome 17), and rs1800682 (Fas) polymorphisms. Furthermore, protective effects against PCOS have been reported for the A4223C polymorphism of adenosine deaminase 1. Overall, the available data indicate that Iranian women with PCOS have a higher prevalence of polymorphisms in inflammation- and metabolism-related genes, but not in insulin-related genes. More extensive studies are needed to identify the ethnicity-related genetic associations in PCOS.

Smoking and hypertension: Effect of adenosine deaminase polymorphism

ABSTRACTAdenosine modulates cardiovascular functions reducing blood pressure and heart rate. Adenosine deaminase (ADA) by the irreversible deamination of adenosine to inosine contributes to the regulation of adenosine concentration in body fluids. We have studied the interaction between smoking and ADA genetic variability concerning their effects on blood pressure.We have studied 344 subjects admitted to the hospital for cardiovascular diseases. The genotypes of two polymorphic loci within the ADA gene were determined: ADA1 and ADA2. Both loci show two alleles: ADA1*1 and ADA1*2 in ADA1 locus and ADA2*1 and ADA2*2 in ADA2 locus.In the absence of smoking, the proportion of subjects with hypertension tends to be lower in carriers of the ADA1*2 allele. In smoking subjects, the pattern is reversed and the proportion of those with hypertension tends to be higher in carriers of the ADA1*2 allele. A similar pattern is observed for ADA2 locus.Smoking increases the proportion of subjects showing hypertension: such effect is more marked in those carrying the ADA1*2 allele as compared to subjects with ADA1*1/*1 genotype. The same pattern of association is observed for ADA2 locus. The two loci show an additive effect. The odds ratio for hypertension in smokers vs nonsmokers is 1.450 in subjects carrying ADA1*1/*1 and ADA2*1/*1 genotypes, while it is 11.200 in subjects carrying the *2 alleles in both loci.From a practical point, a view of our results suggest that smokers carrying both ADA1*2 and ADA2*2 alleles have a higher risk of hypertension.

Relationship between adenosine deaminase polymorphism (c.22G > A) and oxidative stress in sickle cell anemia

The aim of this study was to identify, in people with sickle cell anemia (SCA), adenosine deaminase (ADA; c. 22G>A; rs73598374) polymorphism, and correlating it with oxidative stress markers. We evaluated 95 unrelated and diagnosed Brazilian sickle cell anemia (SCA) patients. All patients received a prophylactic treatment with folic acid of 5mg/day, while 41 (43.2%) of them were under hydroxycarbamide (HC) treatment (average dose: 22mg/kg/day). ADA polymorphism was identified by PCR-RFLP. Biochemical parameters were measured using spectrophotometric [catalase, glutathione S-transferase, glutathione peroxidase, glutathione reductase activities] and chromatographic methods [fetal hemoglobin (HbF), glutathione (GSH) and malondialdehyde (MDA) levels]. Among the 95 SCA patients, we identified 80 (84.2%) wild homozygous for ADA (22GG), 15 (15.8%) heterozygous (22GA) and none mutant homozygous (22AA), leading to an allelic frequency of 0.92 for the ancestral allele (22G) and 0.08 for the mutant one (22A). Unexpectedly, we did not observe any influence of ADA polymorphism on oxidative stress markers, as well as interaction effects with HC usage. However, we confirmed a well-described protective effect of HC treatment on decreasing MDA levels (p=0.03). Thus, we concluded that ADA (22G>A) polymorphism does not play significant role in the disruption of sickle erythrocyte redox metabolism.

Adenosine deaminase polymorphism affects sleep EEG spectral power in a large epidemiological sample.

Slow wave oscillations in the electroencephalogram (EEG) during sleep may reflect both sleep need and intensity, which are implied in homeostatic regulation. Adenosine is strongly implicated in sleep homeostasis, and a single nucleotide polymorphism in the adenosine deaminase gene (ADA G22A) has been associated with deeper and more efficient sleep. The present study verified the association between the ADA G22A polymorphism and changes in sleep EEG spectral power (from C3-A2, C4-A1, O1-A2, and O2-A1 derivations) in the Epidemiologic Sleep Study (EPISONO) sample from São Paulo, Brazil. Eight-hundred individuals were subjected to full-night polysomnography and ADA G22A genotyping. Spectral analysis of the EEG was carried out in all individuals using fast Fourier transformation of the signals from each EEG electrode. The genotype groups were compared in the whole sample and in a subsample of 120 individuals matched according to ADA genotype for age, gender, body mass index, caffeine intake status, presence of sleep disturbance, and sleep-disturbing medication. When compared with homozygous GG genotype carriers, A allele carriers showed higher delta spectral power in Stage 1 and Stages 3+4 of sleep, and increased theta spectral power in Stages 1, 2 and REM sleep. These changes were seen both in the whole sample and in the matched subset. The higher EEG spectral power indicates that the sleep of individuals carrying the A allele may be more intense. Therefore, this polymorphism may be an important source of variation in sleep homeostasis in humans, through modulation of specific components of the sleep EEG.

Functional ADA Polymorphism Increases Sleep Depth and Reduces Vigilant Attention in Humans

Homeostatically regulated slow-wave oscillations in non-rapid eye movement (REM) sleep may reflect synaptic changes across the sleep-wake continuum and the restorative function of sleep. The nonsynonymous c.22G>A polymorphism (rs73598374) of adenosine deaminase (ADA) reduces the conversion of adenosine to inosine and predicts baseline differences in sleep slow-wave oscillations. We hypothesized that this polymorphism affects cognitive functions, and investigated whether it modulates electroencephalogram (EEG), behavioral, subjective, and biochemical responses to sleep deprivation. Attention, learning, memory, and executive functioning were quantified in healthy adults. Right-handed carriers of the variant allele (G/A genotype, n = 29) performed worse on the d2 attention task than G/G homozygotes (n = 191). To test whether this difference reflects elevated homeostatic sleep pressure, sleep and sleep EEG before and after sleep deprivation were studied in 2 prospectively matched groups of G/A and G/G genotype subjects. Deep sleep and EEG 0.75- to 1.5-Hz oscillations in non-REM sleep were significantly higher in G/A than in G/G genotype. Moreover, attention and vigor were reduced, whereas waking EEG alpha activity (8.5-12 Hz), sleepiness, fatigue, and α-amylase in saliva were enhanced. These convergent data demonstrate that genetic reduction of ADA activity elevates sleep pressure and plays a key role in sleep and waking quality in humans.

Effects of the adenosine deaminase polymorphism and caffeine intake on sleep parameters in a large population sample.

To evaluate the association between the adenosine deaminase polymorphism, sleep architecture, and caffeine consumption. Genetic association study. NA. 958 participants who underwent polysomnography and genotyping. NA. Individuals carrying the A allele who consumed caffeine in the day prior to polysomnography demonstrated higher sleep efficiency and REM sleep percentage, after adjustment for potential confounders. No effect was observed in the absence of caffeine. Our data support the role of the ADA G22A polymorphism in sleep, and demonstrate for the first time that caffeine may act as a modulator of its functional effects. Name: Epidemiology of sleep disturbances among adult population of the Sao Paulo City. URL: http://www.clinicaltrials.gov/ct2/show/NCT00596713?term=NCT00596713&rank=1. Number: NCT00596713

A Study of Adenosine-Deaminase Genetic Polymorphism in Rheumatoid Arthritis

Recent investigations suggest that Adenosine Deaminase (ADA) could play a role in susceptibility to rheumatoid arthritis (RA). The purpose of our study is to investigate the possible role of genetic variability of ADA in the susceptibility to RA. We studied three intragenic ADA polymorphisms, ADA1, ADA2 and ADA6, in a sample of 91 subjects with RA and in 246 healthy subjects from the same Caucasian population and compared genotype and pairwise haplotype distributions between cases and controls. No statistically significant differences between RA and controls are observed for ADA genotypes. A border line difference for ADA1-ADA2 haplotype distribution is observed due to a decreased proportion of ADA1 *2/ADA2 *2 haplotype in RA compared to controls. Our data indicate a border line effect of ADA gene polymorphism on susceptibility to RA that need to be confirmed in other clinical settings.

Lower frequency of the low activity adenosine deaminase allelic variant (ADA1*2) in schizophrenic patients

Adenosine may play a role in the pathophysiology of schizophrenia, since it modulates the release of several neurotransmitters such as glutamate, dopamine, serotonin and acetylcholine, decreases neuronal activity by pos-synaptic hyperpolarization and inhibits dopaminergic activity. Adenosine deaminase participates in purine metabolism by converting adenosine into inosine. The most frequent functional polymorphism of adenosine deaminase (22G→A) (ADA1*2) exhibits 20-30% lower enzymatic activity in individuals with the G/A genotype than individuals with the G/G genotype. The aim of this study was to evaluate the ADA polymorphism 22G→A (ADA1*2) in schizophrenic patients and healthy controls. The genotypes of the ADA 22G→A were identified with allele-specific PCR strategy in 152 schizophrenic patients and 111 healthy individuals. A significant decrease in the frequency of the G/A genotype was seen in schizophrenic patients (7/152 - 4.6%) relative to controls (13/111 - 11.7%, p = 0.032, OR = 2.6). These results suggest that the G/A genotype associated with low adenosine deaminase activity and, supposingly, with higher adenosine levels is less frequent among schizophrenic patients.

Thesis Abstract Evaluation of angiotensin-converting enzyme and adenosine deaminase polymorphisms in patients with type 2 diabetes mellitus

Thesis Abstract Evaluation of angiotensin-converting enzyme and adenosine deaminase polymorphisms in patients with type 2 diabetes mellitus

The genetics of feto-placental development: A study of acid phosphatase locus 1 and adenosine deaminase polymorphisms in a consecutive series of newborn infants

BackgroundAcid phosphatase locus 1 and adenosine deaminase locus 1 polymorphisms show cooperative effects on glucose metabolism and immunological functions. The recent observation of cooperation between the two systems on susceptibility to repeated spontaneous miscarriage prompted us to search for possible interactional effects between these genes and the correlation between birth weight and placental weight. Deviation from a balanced development of the feto-placental unit has been found to be associated with perinatal morbidity and mortality and with cardiovascular diseases in adulthood.MethodsWe examined 400 consecutive newborns from the Caucasian population of Rome. Birth weight, placental weight, and gestational length were registered. Acid phosphatase locus 1 and adenosine deaminase locus 1 phenotypes were determined by starch gel electrophoresis and correlation analysis was performed by SPSS programs. Informed verbal consent to participate in the study was obtained from the mothers.ResultsHighly significant differences in birth weight-placental weight correlations were observed among acid phosphatase locus 1 phenotypes (p = 0.005). The correlation between birth weight and placental weight was markedly elevated in subjects carrying acid phosphatase locus 1 phenotypes with medium-low F isoform concentration (A, CA and CB phenotypes) compared to those carrying acid phosphatase locus 1 phenotypes with medium-high F isoform concentration (BA and B phenotypes) (p = 0.002). Environmental and developmental variables were found to exert a significant effect on birth weight-placental weight correlation in subjects with medium-high F isoform concentrations, but only a marginal effect was observed in those with medium-low F isoform concentrations. The correlation between birth weight and placental weight is higher among carriers of the adenosine deaminase locus 1 allele*2, which is associated with low activity, than in homozygous adenosine deaminase locus 1 phenotype 1 carriers (p = 0.04). The two systems show a cooperative effect on the correlation between birth weight and placental weight: the highest value is observed in newborns carrying adenosine deaminase locus 1 allele*2 and acid phosphatase locus 1 phenotypes with medium-low F isoform concentration (p = 0.005).ConclusionThese data suggest that zygotes with low adenosine deaminase locus 1 activity and low F activity may experience the most favourable intrauterine conditions for a balanced development of the feto-placental unit.

Further data on adenosine deaminase polymorphism in pigs and evidence for a new allele

Evidence was provided for a new erythrocyte ADA allele (Aw) in the Swedish Landrace breed of pigs. The enzyme activity of Aw variant was considerably less than that of the previously reported erythrocyte ADA variants A and B. The mobility of the Aw variant was identical to that of the A variant, both by electrophoresis and by isoelectric focusing. The in vitro heat stability (at 56 degrees C) of the Aw variant was similar to that of A and B variants. The leucocyte ADA activity was normal in pigs with the erythrocyte ADA Aw variant. The frequencies of the erythrocyte ADA alleles, A, B, Aw, and O (silent allele) in four breeds of pigs in Sweden were: Landrace--0.51, 0.19, 0.11, 0.19; Large White--0.91, 0.03, 0.0, 0.06; Duroc--0.95, 0.05, 0.0, 0.0; Hampshire--0.12, 0.14, 0.0, 0.74.

Adenosine deaminase polymorphism in Finnish Landrace pigs.

Phenotypes of the enzyme adenosine deaminase were determined in red cells from 1289 pigs from the elite breeding herds of the Finnish Landrace breed. The recessive O type was found in 16.7% of the animals. The gene frequencies were estimated to qA=0.37, qB=0.20 and qO=0.43. Among the pigs (144) selected by the breeders for their own herd, the occurrence of the O type (13.9%) did not deviate significantly from that in the total material. There were no indications that the O type of ADA was disfavoured in the selection of breeding animals of the Finnish Landrace breed.

ADA*2 Allele of the Adenosine Deaminase Gene May Protect against Coronary Artery Disease

Background/Aims: The common G22A polymorphism in the adenosine deaminase (ADA) gene leads to substitution Asp8Asn. The lower activity of the enzyme encoded by A22 (ADA*2) allele may increase tissue concentrations of adenosine, a potent cardioprotective agent. In a case-control study, we investigated the association between ADA polymorphism and coronary artery disease (CAD). Methods: A hundred and seventy-one CAD patients from the north-western part of Poland and 200 consecutive newborns from the same population were genotyped by PCR-RFLP. Results: Twenty-five ADA*1/*2 heterozygotes (12.5%) and 2 ADA*2/*2 homozygotes (1%) were found in the control group, while only 10 *1/*2 heterozygotes (5.9%) and no *2/*2 homozygotes were found in the CAD group. Frequencies of ADA*2 carriers (5.9% vs. 13.5%, p = 0.015) and ADA*2 allele (2.9% vs. 7.3%, p = 0.0083) were lower in CAD patients than in controls. Among CAD patients, a significantly lower proportion of *2 allele carriers was treated with diuretics and ACE inhibitors when compared to *1/*1 wild-type homozygotes. Conclusion: ADA*2 allele may decrease genetic susceptibility to CAD. ADA should be added to the list of candidate genes modifying the risk of cardiovascular diseases.

Association of Adenosine Deaminase Polymorphism With Mild Mental Retardation

The etiology of mild mental retardation remains undefined in about 60% of cases. Even though the causes of mild mental retardation are likely to be heterogeneous, the evidence for genetic involvement is increasing, along with the development of specific diagnostic techniques. To improve our understanding of the genetic basis of mild mental retardation, we explored the role of polymorphisms of adenosine deaminase, an enzyme that is supposed to act as a neuroregulatory protein. To this end, we conducted an association study comparing children with mild mental retardation of unknown origin with two groups of controls: (1) apparently healthy children and (2) children with moderate or severe mental retardation of known etiology. Overall, 338 participants were enrolled in the study. Cases (ie, 80 children) were more likely than controls (ie, 153 healthy children and 105 children with moderate or severe mental retardation) to have the low-activity ADA-Asn 8 (ADA(1) *2) polymorphism (P < .05) and to present the ADA(1) *2/ ADA(2) *1 haplotype. No significant differences were found with respect to adenosine deaminase polymorphisms when comparing the group with moderate or severe mental retardation of known causes and healthy controls. In conclusion, our findings suggest a possible role for a low-activity genotype (ADA-8Asn) (ADA(1) *2) of adenosine deaminase in the pathogenesis of mild mental retardation.

Genetic polymorphism of adenosine deaminase (ADA; E.C. 3.5.4.4.) in allis shad, Alosa alosa and twaite shad, Alosa fallax

A genetic polymorphism of adenosine deaminase (ADA), is described for the first time in European shad species, Alosa alosa and Alosa fallax. Significant heterogeneity in gene frequencies was found, both between species and within species.

Genetic polymorphism of adenosine deaminase and mannose phosphate isomerase in blood of arctic foxes, Alopex lagopus

Blood samples of 70 foxes, including 10 families, have been investigated by horizontal starch gel electrophoresis for the enzymes adenosine deaminase (ADA) and mannose phosphate isomerase (MPI). The observed variation of the enzymes could be explained as a result of one locus with two codominant alleles and one with three respectively. The segregation in the families of the alleles assumed for the two loci is in accordance with this genetic model. The frequency of the two alleles at the Ada locus is about the same and the slowest anodic migrating allele at the Mpi locus is the most frequent.

Polymorphism of Red Cell Adenosine Deaminase by Cellogel Electrophoresis in Rabbits

Using cellogel electrophoresis, polymorphism of adenosine deaminase (ADA) was found in haemolysed rabbit erythrocytes. In this study, six different phenotypes A, B, C, AB, AC and BC were observed. It was confirmed from family data that these phenotypes were determined by three codominant alleles ADAA ADAB and ADAC.

Adenosine deaminase polymorphism. Associations at clinical level suggest a role in cell functions and immune reactions.

It is well known that subjects homozygous for a rare silent allele of ADA may experience a severe combined immunodeficiency. By analogy we have investigated the possible relationship of normal ADA polymorphism with some situations, such as reproductive defects and fetomaternal interactions, in which immunological mechanisms may play an important role. A total of 572 consecutive newborns, 93 consecutive low birthweight infants, 46 couples with unexplained habitual abortion, and 24 couples with unexplained sterility were studied. The proportion of ADA 2-1 phenotype was reduced in couples with reproductive defects. In the sample of consecutive newborns the proportion of ABO incompatible babies was higher among ADA 2-1 than among ADA 1 types. ADA 2-1 phenotype was also associated with a reduction in the variability of gestational length. These associations were much more marked among male than among female babies. The proportion of ADA 2-1 was significantly lower in low birthweight infants than in the consecutively studied infants and normal adults. The present data suggest that biochemical variability resulting from the normal ADA polymorphism may be, at least in part, responsible for the variability of some immunological functions and related physiological variables and pathological conditions. They also provide evidence in favour of a selective advantage of ADA heterozygotes.

Serum albumin and erythrocyte adenosine deaminase polymorphisms in Asian macaques with special reference to taxonomic relationships amongMacaca assamensis,M. radiata, andM. mulatta

Serum albumin (Alb) and erythrocyte adenosine deaminase (ADA) polymorphisms in Asian macaques were investigated by means of starch gel electrophoresis. The materials comprise a total of 2,323 blood samples from eight species, namely,Macaca fuscata,M. mulatta,M. cyclopis,M. fascicularis,M. nemestrina,M. speciosa,M. radiata, andM. assamensis. It was observed that three Alb phenotypes were controlled by two codominant alleles, Alb mac A and Alb mac B and six ADA phenotypes by four codominant alleles, ADA mac 1 , ADA mac 2 , ADA mac 3 , and ADA mac 4 . The taxonomic relationships amongM. assamensis,M. radiata, andM. mulatta were analyzed by measuring theNei's (1975) genetic distance. The result supportedHill andBernstein's (1969) postulation thatM. assamensis was more closely related phylogenetically toM. radiata than toM. mulatta.