Deaminase Polymorphism Research Articles

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.

Pharmacokinetics of Gemcitabine in Japanese Cancer Patients: The Impact of a Cytidine Deaminase Polymorphism

Gemcitabine is rapidly metabolized to its inactive metabolite, 2',2'-difluorodeoxyuridine (dFdU), by cytidine deaminase (CDA). We previously reported that a patient with homozygous 208A alleles of CDA showed severe adverse reactions with an increase in gemcitabine plasma level. This study extended the investigation of the effects of CDA genetic polymorphisms on gemcitabine pharmacokinetics and toxicities. Genotyping of CDA was performed by a direct sequencing of DNA obtained from the peripheral blood of Japanese gemcitabine-naïve cancer patients (n = 256). The patients recruited to the association study received a 30-minute intravenous infusion of gemcitabine at a dose of either 800 or 1,000 mg/m2, and eight blood samples were periodically collected (n = 250). Plasma levels of gemcitabine and dFdU were measured by high-performance liquid chromatography. Plasma CDA activities toward cytidine and gemcitabine were also measured (n = 121). Twenty-six genetic variations, including 14 novel ones and two known nonsynonymous single nucleotide polymorphisms (SNPs), were detected. Haplotypes harboring the nonsynonymous SNPs 79A>C (Lys27Gln) and 208G>A (Ala70Thr) were designated *2 and *3, respectively. The allelic frequencies of the two SNPs were 0.207 and 0.037, respectively. Pharmacokinetic parameters of gemcitabine and plasma CDA activities significantly depended on the number of haplotype *3. Haplotype *3 was also associated with increased incidences of grade 3 or higher neutropenia in the patients who were coadministered fluorouracil, cisplatin, or carboplatin. Haplotype *2 showed no significant effect on gemcitabine pharmacokinetics. Haplotype *3 harboring a nonsynonymous SNP, 208G>A (Ala70Thr), decreased clearance of gemcitabine, and increased incidences of neutropenia when patients were coadministered platinum-containing drugs or fluorouracil.

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.

Adaptation to past malarial endemia and susceptibility to common diseases in modern populations: A study of adenosine deaminase and MN blood group genetic polymorphisms

We carried out a study of adenosine deaminase (ADA) and MN blood group genetic polymorphisms in relation to past malarial morbidity in Sardinia and in relation to susceptibility to allergic asthma (a Th2 disorder) and Crohn's disease (a Th1 disorder) in the population of Rome. Eight hundred and eight schoolchildren, aged 7--14 years from 14 Sardinian villages located in the central area of the island, were considered. One hundred and twenty-two children with allergic asthma and 39 adult patients with Crohn's disease from the population of Rome were also studied. The data suggest an interaction between the two systems concerning resistance/susceptibility, both to malaria and to the diseases considered. In Sardinia, the frequency of the *L(M)/ADA*2 gametic type is negatively correlated with past malarial endemia, suggesting an increased susceptibility to malaria leading to its decrease in areas with high malarial endemia. In Rome, this gametic type is correlated negatively to allergic asthma and positively to Crohn's disease, suggesting a protective effect against allergic asthma and increased susceptibility to Crohn's disease.

Association of an adenosine monophosphate deaminase (AMPD) polymorphism and recovery of normal ventricular function in patients with dilated cardiomyopathy

Association of an adenosine monophosphate deaminase (AMPD) polymorphism and recovery of normal ventricular function in patients with dilated cardiomyopathy

Evidence of selective interaction between adenosine deaminase and acid phosphatase polymorphisms in fetuses carried by diabetic women

Possible selective interaction between genetic polymorphisms of acid phosphatase locus 1 (ACP1) and adenosine deaminase (ADA) has been investigated in a sample of 211 infants from diabetic women, and in 350 consecutive infants from normal women. Newborns from diabetic pregnancies carrying the ADA2 allele show a lower proportion of BA and CB phenotypes (heterozygotes for the main allele of ACP1 system), compared with both their mothers and normal infants. The observation suggests that, in a diabetic environment, intrauterine selection may act against double heterozygotes for the ACP1 and ADA systems.

Adenosine deaminase, adenylate kinase and acid phosphatase polymorphism in a French-Canadian population.

Adenosine deaminase (ADA), adenylate kinase (AK1), and acid phosphatase (ACP1) red blood cell enzymes were studied for allelic variation in a French-Canadian population from Quebec City, Canada. Allele frequencies in 887 unrelated individuals were for ACP1, ACP1*A: 0.305; ACP1*B: 0.635 and ACP1*C: 0.060, for ADA, ADA*1: 0.969, ADA*2: 0.031, and for AK1, AK1*1: 0.976, AK1*2: 0.024. The allele frequencies for each enzyme were identical to those previously reported in other Caucasian populations.

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.

Red cell adenosine deaminase (ADA) polymorphism in Southern Africa, with special reference to ADA deficiency among the !Kung.

Studies have been carried out on polymorphism of adenosine deaminase in 36 Southern African populations comprising more than 3000 individuals. The common variant allele ADA2 has been found to attain polymorphic frequencies only in those populations descended from non-indigenous (i.e. non-Negro and non-Khoisan) groups. Its presence in certain other populations at low frequencies could be ascribed to small-scale Caucasoid admixture. A deficiency of the enzyme is found in certain members of the !Kung division of the San ('Bushman'). The low levels of enzyme activity are not associated with severe combined immunodeficiency and the gene which determines them appears to be polymorphic in the !Kung and possibly in some other San populations as well as possibly in Negro populations which have received substantial contributions of San genes.

Studies on adenosine deaminase (ADA) polymorphism in Danish cattle.

Animal Blood Groups and Biochemical GeneticsVolume 9, Issue 3 p. 191-193 Studies on adenosine deaminase (ADA) polymorphism in Danish cattle1 B. Larsen, B. Larsen Department of Physiology, Endocrinology and Bloodgrouping, Royal Veterinary and Agricultural University, Copenhagen, DenmarkSearch for more papers by this authorJ. Hyldgaard-Jensen, J. Hyldgaard-Jensen Department of Physiology, Endocrinology and Bloodgrouping, Royal Veterinary and Agricultural University, Copenhagen, DenmarkSearch for more papers by this authorLise Aagaard, Lise Aagaard Department of Physiology, Endocrinology and Bloodgrouping, Royal Veterinary and Agricultural University, Copenhagen, DenmarkSearch for more papers by this author B. Larsen, B. Larsen Department of Physiology, Endocrinology and Bloodgrouping, Royal Veterinary and Agricultural University, Copenhagen, DenmarkSearch for more papers by this authorJ. Hyldgaard-Jensen, J. Hyldgaard-Jensen Department of Physiology, Endocrinology and Bloodgrouping, Royal Veterinary and Agricultural University, Copenhagen, DenmarkSearch for more papers by this authorLise Aagaard, Lise Aagaard Department of Physiology, Endocrinology and Bloodgrouping, Royal Veterinary and Agricultural University, Copenhagen, DenmarkSearch for more papers by this author First published: August 1978 https://doi.org/10.1111/j.1365-2052.1978.tb01435.x Supported by grant from Danish Agricultural and Veterinary Research Council. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume9, Issue3August 1978Pages 191-193 RelatedInformation

Adenosine deaminase polymorphism among the Semai, Temuan, Semelai, and Jakun groups of West Malaysian Orang Asli.

812 West Malaysian Orang Asli belonging to four ethnic groups were surveyed for adenosine deaminase (ADA; EC 3.5.4.4) using starch gel electrophoresis. Only the common ADA1 and ADA2 alleles were found, with the frequencies of the latter being 0.025, 0.103, 0.115 and 0.028 in the Semai, Semelai, Temuan, and Jakun groups, respectively. A new 'breeding genetic distance' was applied to these gene frequencies and the Semelai and Temuan were found to be more closely related to each other, and to have considerably more evolutionary flexibility on this scale of 'micro-evolution' than the other two groups. The Semai and Jakun were more similar to each other on the basis of these ADA gene frequencies.

Frequency of red cell adenosine deaminase and 6-phosphogluconate dehydrogenase in a sample of the Turkish population.

The adenosine deaminase (ADA) and 6-phosphogluconate dehydrogenase (6-PGD) polymorphisms were examined in cord blood samples of Turkish neonates. The frequency of the genes ADA2 and 6-PGD

Adenosine Deaminase Polymorphism in a Swedish Population

SummaryAdenosine deaminase (ADA) isoenzymes in a Swedish population of 342 unrelated individuals have been determined according to the method of Spencer et al. (1968). The gene frequencies found were 0.9357 and 0.0643 for ADA 1 and ADA 2 respectively. These frequencies are in good accordance with previous investigations.

Adenosine deaminase (ADA) polymorphism in Northern England.

Adenosine deaminase gene frequencies in two subsamples from Northumberland (North England) show no local variation but suggest possible differences from the south of England.

Adenosine deaminase in lymphocytes and its electrophoretic separation.

The adenosine deaminase polymorphism was found in lymphocyte lysates. Lymphocytes exhibited an additional ADA isozyme distinguished from other ADA isozymes by its lack of free -SH groups. It was suggested that this new isozyme is controlled by a second genetic locus.

Human erythrocyte adenosine deaminase polymorphism in Denmark.

The ADA types of human red cells are reported for a material of 1321 unrelated adults in Denmark. The gene frequencies observed are: ADA1 = 0.9391 and ADA2 = 0.0609. The study of 754 mother-child pairs provides further evidence for a simple Mendelian codominant way of inheritance.

Further data on the adenosine deaminase (ADA) polymprphism and a report of a new phenotype.

Further data on the adenosine deaminase (ADA) polymprphism and a report of a new phenotype.